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Matsumoto N, Mitsui T, Tamai K, Hirota T, Masuyama H, Yorifuji T. Cesarean delivery on child health and development in Japanese nationwide birth cohort. Sci Rep 2025; 15:2485. [PMID: 39833288 PMCID: PMC11747486 DOI: 10.1038/s41598-025-87043-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 01/15/2025] [Indexed: 01/22/2025] Open
Abstract
The long-term effects of cesarean delivery (CD) on child health and development remain controversial. This study aimed to investigate these effects using an outcome-wide approach in a Japanese context, where perinatal mortality rates are among the world's lowest. We analyzed data from 2,114 children in a nationwide Japanese birth cohort, linking the 21st Century Longitudinal Survey of Newborns with the Perinatal Research Network database. We examined associations between CD and various health and developmental outcomes up to 9 years of age, including hospitalizations, obesity, and developmental milestones. After adjusting for potential confounders, CD was not significantly associated with most outcomes, including all-cause hospitalization (adjusted risk ratio 1.25, 95% CI 0.997-1.56), obesity at 5.5 and 9 years, and various developmental milestones. Subgroup analyses for multiple births and preterm infants showed some differences in point estimates, but were limited by small sample sizes. CD was not significantly associated with adverse long-term child health or developmental outcomes in this Japanese cohort. These findings provide reassurance regarding CD safety when medically indicated in advanced perinatal care settings. Further research with larger samples and longer follow-up is needed, especially for specific subgroups.
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Affiliation(s)
- Naomi Matsumoto
- Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita- ku, Okayama, Japan.
| | - Takashi Mitsui
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Kei Tamai
- Division of Neonatology, NHO Okayama Medical Center, Okayama, Japan
| | - Tomoya Hirota
- Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, USA
| | - Hisashi Masuyama
- Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Okayama, Japan
| | - Takashi Yorifuji
- Department of Epidemiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita- ku, Okayama, Japan
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Di Miceli M, Rossitto M, Martinat M, Marchaland F, Kharbouche S, Graland M, Younes F, Séré A, Aubert A, Khabbaz LR, Madore C, Delpech JC, Martín R, Layé S. Modified neuroimmune processes and emotional behaviour in weaned and late adolescent male and female mice born via caesarean section. Sci Rep 2024; 14:29807. [PMID: 39616177 PMCID: PMC11608364 DOI: 10.1038/s41598-024-80770-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Accepted: 11/21/2024] [Indexed: 02/07/2025] Open
Abstract
Elective and emergency Caesarean section (C-section) procedures are on the rise, exceeding the recommended guidelines by the World Health Organization. Higher morbidities and long-term health conditions are correlated to C-section deliveries, including neurodevelopmental disorders. During C-section delivery, newborns are not exposed to the vaginal commensal flora, which impedes the early establishment of the gut microbiota. The latter is essential for adequate neuro-immune processes to take place during infancy. In this study, we used a validated model of mice born by C-section (CSD), which mimics clinical observations of dysregulated gut microbiota. Animals were either born naturally or by CSD, before being adopted by dams who underwent delivery within the 12 preceding hours. Behavioural analyses were conducted at post-natal day (PND) 21 and 55. Our results indicate that animals born by C-section present significantly higher body weight in late (PND40-P53) but not early adolescence (PND21-P27), compared to animals born by vaginal delivery (VD). Male animals delivered by C-section presented significantly lower exploration time of the novel arm in the Y Maze test at PND55. However, at PND21, abnormal social interaction was witnessed in male and female animals born by CSD, with significantly decreased time spent interacting during the social interaction test. At both PND21 and PND55, animals from both sexes born by C-section presented significantly decreased time spent in the open arm of the Elevated Plus Maze test, compared to control animals. We then measured the expression of genes associated to neuroimmune interactions (microglia phenotype), inflammatory mediators and lipids in several brain structures of VD and CSD mice at PND21 and PND55. At weaning, animals born by CSD presented altered microglia, inflammatory and lipid metabolism signatures, with increased expression of Cd36, Csf1r and Tnfα in different brain regions of males, but not in females. At PND64, Csf1r, Tmem119 as well as C3ar1 were significantly increased in males born by C-section, but not in females. In males born by vaginal delivery, the expression of Cd36 at PND64 was correlated to anxiety at PND55, whilst a correlation between the expression of Clec7a and the number of head dippings in the elevated plus maze was also noted in males born by CSD. Altogether, our study shows altered emotional behaviour in animals delivered by CSD, which is likely explained by underlying neuro-inflammatory processes in different brain regions. Our work further supports the long-term consequences of CSD on brain health.
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Affiliation(s)
- Mathieu Di Miceli
- Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France.
- Worcester Biomedical Research Group, School of Science and the Environment, University of Worcester, Henwick Grove, Worcester, WR2 6AJ, UK.
- Faculty of Biological Sciences, School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK.
| | - Moïra Rossitto
- Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | - Maud Martinat
- Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | - Flore Marchaland
- Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | - Sarah Kharbouche
- Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | - Marion Graland
- Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | - Farah Younes
- Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | - Alexandra Séré
- Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | - Agnès Aubert
- Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | - Lydia Rabbaa Khabbaz
- Laboratoire de Pharmacologie, Pharmacie Clinique et Contrôle de Qualité des Médicaments, Faculty of Pharmacy, Saint-Joseph University of Beirut, Beirut, Lebanon
| | - Charlotte Madore
- Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | | | - Rebeca Martín
- Micalis Institute, AgroParisTech, INRAE, Université Paris-Saclay, 78350, Jouy-En-Josas, France
| | - Sophie Layé
- Université de Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
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Chen M, Zhou Y. Causal mediation analysis with a three-dimensional image mediator. Stat Med 2024; 43:2869-2893. [PMID: 38733218 DOI: 10.1002/sim.10106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 03/20/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024]
Abstract
Causal mediation analysis is increasingly abundant in biology, psychology, and epidemiology studies and so forth. In particular, with the advent of the big data era, the issue of high-dimensional mediators is becoming more prevalent. In neuroscience, with the widespread application of magnetic resonance technology in the field of brain imaging, studies on image being a mediator emerged. In this study, a novel causal mediation analysis method with a three-dimensional image mediator is proposed. We define the average casual effects under the potential outcome framework, explore several sufficient conditions for the valid identification, and develop techniques for estimation and inference. To verify the effectiveness of the proposed method, a series of simulations under various scenarios is performed. Finally, the proposed method is applied to a study on the causal effect of mother's delivery mode on child's IQ development. It is found that cesarean section may have a negative effect on intellectual performance and that this effect is mediated by white matter development. Additional prospective and longitudinal studies may be necessary to validate these emerging findings.
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Affiliation(s)
- Minghao Chen
- Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE, School of Statistics, East China Normal University, Shanghai, People's Republic of China
| | - Yingchun Zhou
- Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE, School of Statistics, East China Normal University, Shanghai, People's Republic of China
- Institute of Brain and Education Innovation, East China Normal University, Shanghai, People's Republic of China
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Bobba PS, Weber CF, Malhotra A, Bahtiyar MO, Copel J, Taylor SN, Ment LR, Payabvash S. Early brain microstructural development among preterm infants requiring caesarean section versus those delivered vaginally. Sci Rep 2023; 13:21514. [PMID: 38057452 PMCID: PMC10700578 DOI: 10.1038/s41598-023-48963-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Accepted: 12/01/2023] [Indexed: 12/08/2023] Open
Abstract
It is known that the rate of caesarean section (C-section) has been increasing among preterm births. However, the relationship between C-section and long-term neurological outcomes is unclear. In this study, we utilized diffusion tensor imaging (DTI) to characterize the association of delivery method with brain white matter (WM) microstructural integrity in preterm infants. We retrospectively analyzed the DTI scans and health records of preterm infants without neuroimaging abnormality on pre-discharge term-equivalent MRI. We applied both voxel-wise and tract-based analyses to evaluate the association between delivery method and DTI metrics across WM tracts while controlling for numerous covariates. We included 68 preterm infants in this study (23 delivered vaginally, 45 delivered via C-section). Voxel-wise and tract-based analyses revealed significantly lower fractional anisotropy values and significantly higher diffusivity values across major WM tracts in preterm infants delivered via C-section when compared to those delivered vaginally. These results may be partially, but not entirely, mediated by lower birth weight among infants delivered by C-section. Nevertheless, these infants may be at risk for delayed neurodevelopment and could benefit from close neurological follow up for early intervention and mitigation of adverse long-term outcomes.
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Affiliation(s)
- Pratheek S Bobba
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 789 Howard Ave, PO Box 208042, New Haven, CT, 06519, USA
| | - Clara F Weber
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 789 Howard Ave, PO Box 208042, New Haven, CT, 06519, USA
- Social Neuroscience Lab, Department of Psychiatry and Psychotherapy, Lübeck University, Lübeck, Germany
| | - Ajay Malhotra
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 789 Howard Ave, PO Box 208042, New Haven, CT, 06519, USA
| | - Mert O Bahtiyar
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
| | - Joshua Copel
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
- Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
| | - Sarah N Taylor
- Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
| | - Laura R Ment
- Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
- Department of Neurology, Yale School of Medicine, New Haven, CT, USA
| | - Seyedmehdi Payabvash
- Department of Radiology and Biomedical Imaging, Yale School of Medicine, 789 Howard Ave, PO Box 208042, New Haven, CT, 06519, USA.
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Bobba PS, Weber CF, Malhotra A, Bahtiyar MO, Copel J, Taylor SN, Ment LR, Payabvash S. Early brain microstructural development among preterm infants requiring caesarean section versus those delivered vaginally. RESEARCH SQUARE 2023:rs.3.rs-3389209. [PMID: 37886582 PMCID: PMC10602105 DOI: 10.21203/rs.3.rs-3389209/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/28/2023]
Abstract
It is known that the rate of caesarean section (C-section) has been increasing among preterm births. However, the relationship between C-section and long-term neurological outcomes is unclear. In this study, we utilized diffusion tensor imaging (DTI) to characterize the association of delivery method with brain white matter (WM) microstructural integrity in preterm infants. We retrospectively analyzed the DTI scans and health records of preterm infants without neuroimaging abnormality on pre-discharge term-equivalent MRI. We applied both voxel-wise and tract-based analyses to evaluate the association between delivery method and DTI metrics across WM tracts while controlling for numerous covariates. We included 68 preterm infants in this study (23 delivered vaginally, 45 delivered via C-section). Voxel-wise and tract-based analyses revealed significantly lower fractional anisotropy values and significantly higher diffusivity values across major WM tracts in preterm infants delivered via C-section when compared to those delivered vaginally. These results may be partially, but not entirely, mediated by lower birth weight among infants delivered by C-section. Nevertheless, these infants may be at risk for delayed neurodevelopment and could benefit from close neurological follow up for early intervention and mitigation of adverse long-term outcomes.
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Zhang Y, Zhou CY, Wang XR, Jiao XT, Zhang J, Tian Y, Li LL, Chen C, Yu XD. Maternal and neonatal blood vitamin D status and neurodevelopment at 24 months of age: a prospective birth cohort study. World J Pediatr 2023; 19:883-893. [PMID: 36972015 DOI: 10.1007/s12519-022-00682-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Accepted: 12/29/2022] [Indexed: 06/18/2023]
Abstract
BACKGROUND This study aimed to explore the relationship of 25-hydroxyvitamin D [25(OH)D] in three trimesters and at birth with neurodevelopment at 24 months of age. METHODS From 2013 to 2016, pregnant women from the Shanghai Birth Cohort in China were recruited for the study. Altogether, 649 mother-infant pairs were included. Serum 25(OH)D was measured with mass spectrometry in three trimesters, and cord blood was divided into deficiency (< 20 and < 12 ng/mL, respectively), insufficiency (20-30 and 12-20 ng/mL, respectively), and sufficiency (≥ 30 and ≥ 20 ng/mL, respectively). Bayley-III scale was used to assess cognitive, language, motor, social-emotional, and adaptive behavior development at 24 months of age. The Bayley-III scores were grouped into quartiles, and scores within the lowest quartile were defined as suboptimal development. RESULTS After adjusting for confounding factors, cord blood 25(OH)D in the sufficient group was positively correlated with cognitive [β = 11.43, 95% confidence interval (CI) = 5.65-17.22], language (β = 6.01, 95% CI = 1.67-10.3), and motor scores (β = 6.43, 95% CI = 1.73-11.1); cord blood 25(OH)D in the insufficient group was also positively correlated with cognitive scores (β = 9.42, 95% CI = 3.74-15.11). Additionally, sufficient vitamin D status in the four periods and persistent 25(OH)D ≥ 30 ng/mL throughout pregnancy were associated with a lower risk of suboptimal cognitive development in adjusted models, although the effects were attenuated after applying the false discovery rate adjustment. CONCLUSIONS Cord blood 25(OH)D ≥ 12 ng/mL has a significant positive association with cognitive, language, and motor development at 24 months of age. Sufficient vitamin D status in pregnancy might be a protective factor for suboptimal neurocognition development at 24 months of age.
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Affiliation(s)
- Yue Zhang
- Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Chun-Yan Zhou
- Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Xi-Rui Wang
- Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Xian-Ting Jiao
- MOE-Shanghai Key Lab of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Jun Zhang
- MOE-Shanghai Key Lab of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Ying Tian
- MOE-Shanghai Key Lab of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Luan-Luan Li
- Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Chen Chen
- Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Xiao-Dan Yu
- Department of Developmental and Behavioral Pediatrics, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
- MOE-Shanghai Key Lab of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
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7
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Yoshida T, Matsumura K, Hatakeyama T, Inadera H. Association between Cesarean section and neurodevelopmental disorders in a Japanese birth cohort: the Japan Environment and Children's Study. BMC Pediatr 2023; 23:306. [PMID: 37331958 DOI: 10.1186/s12887-023-04128-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 06/12/2023] [Indexed: 06/20/2023] Open
Abstract
BACKGROUND The long-term effects of a Cesarean section (CS) birth on child neurodevelopment are of increasing interest. In this study, we examined the associations between mode of delivery and presence of neurodevelopmental disorders in toddlers. Moreover, given that the prevalence of several neurodevelopmental disorders such as autism spectrum disorder (ASD) is known to differ by sex, we also investigated these associations separately in male and female toddlers. METHODS We investigated 65,701 mother-toddler pairs from the Japan Environment and Children's Study, a nationally representative children's cohort study. To investigate the associations between mode of delivery (CS or vaginal delivery) and neurodevelopmental disorders (motor delay, intellectual disability, and ASD) in 3-year-old toddlers as a whole and stratified by sex, we used logistic regression models to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS The morbidity of ASD at age 3 years was higher for children delivered by CS than those delivered vaginally (aOR 1.38, 95% CI 1.04-1.83). However, no such difference was evident in the case of motor delay or intellectual disability (aOR 1.33, 95% CI 0.94-1.89; aOR 1.18, 95% CI 0.94-1.49, respectively). In the analysis by sex, CS was not associated with increased risk of any of the neurodevelopmental disorders in males, but it was associated with increased risks of motor delay (aOR 1.88, 95% CI 1.02-3.47) and ASD (aOR 1.82, 95% CI 1.04-3.16) in females. CONCLUSIONS This study provides evidence of significant associations between mode of delivery and neurodevelopmental disorders in early childhood. Females may be more sensitive to the effects of CS than males.
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Affiliation(s)
- Taketoshi Yoshida
- Division of Neonatology, Maternal and Perinatal Center, Toyama University Hospital, 2630 Sugitani, Toyama City, 930-0194, Japan.
| | - Kenta Matsumura
- Department of Public Health, Faculty of Medicine, University of Toyama, Toyama, Japan
- Toyama Regional Center for JECS, University of Toyama, Toyama, Japan
| | | | - Hidekuni Inadera
- Department of Public Health, Faculty of Medicine, University of Toyama, Toyama, Japan
- Toyama Regional Center for JECS, University of Toyama, Toyama, Japan
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Kenkel WM, Ortiz RJ, Yee JR, Perkeybile AM, Kulkarni P, Carter CS, Cushing BS, Ferris CF. Neuroanatomical and functional consequences of oxytocin treatment at birth in prairie voles. Psychoneuroendocrinology 2023; 150:106025. [PMID: 36709631 PMCID: PMC10064488 DOI: 10.1016/j.psyneuen.2023.106025] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 01/06/2023] [Accepted: 01/07/2023] [Indexed: 01/15/2023]
Abstract
Birth is a critical period for the developing brain, a time when surging hormone levels help prepare the fetal brain for the tremendous physiological changes it must accomplish upon entry into the 'extrauterine world'. A number of obstetrical conditions warrant manipulations of these hormones at the time of birth, but we know little of their possible consequences on the developing brain. One of the most notable birth signaling hormones is oxytocin, which is administered to roughly 50% of laboring women in the United States prior to / during delivery. Previously, we found evidence for behavioral, epigenetic, and neuroendocrine consequences in adult prairie vole offspring following maternal oxytocin treatment immediately prior to birth. Here, we examined the neurodevelopmental consequences in adult prairie vole offspring following maternal oxytocin treatment prior to birth. Control prairie voles and those exposed to 0.25 mg/kg oxytocin were scanned as adults using anatomical and functional MRI, with neuroanatomy and brain function analyzed as voxel-based morphometry and resting state functional connectivity, respectively. Overall, anatomical differences brought on by oxytocin treatment, while widespread, were generally small, while differences in functional connectivity, particularly among oxytocin-exposed males, were larger. Analyses of functional connectivity based in graph theory revealed that oxytocin-exposed males in particular showed markedly increased connectivity throughout the brain and across several parameters, including closeness and degree. These results are interpreted in the context of the organizational effects of oxytocin exposure in early life and these findings add to a growing literature on how the perinatal brain is sensitive to hormonal manipulations at birth.
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Affiliation(s)
- William M Kenkel
- Department of Psychological & Brain Sciences, University of Delaware, Newark, DE, USA; Department of Psychology, Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA.
| | - Richard J Ortiz
- Department of Psychology, Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA; Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM, USA; Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA
| | - Jason R Yee
- Department of Psychology, Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA; Institute of Animal Welfare Science, University of Veterinary Medicine, Vienna, Austria
| | - Allison M Perkeybile
- Department of Psychology, Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA; Department of Psychology, University of Virginia, Charlottesville, VA, USA
| | - Praveen Kulkarni
- Department of Psychology, Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA
| | - C Sue Carter
- Department of Psychology, University of Virginia, Charlottesville, VA, USA
| | - Bruce S Cushing
- Department of Biological Sciences, University of Texas at El Paso, El Paso, TX, USA
| | - Craig F Ferris
- Department of Psychology, Center for Translational NeuroImaging, Northeastern University, Boston, MA, USA
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Sharvin BL, Aburto MR, Cryan JF. Decoding the neurocircuitry of gut feelings: Region-specific microbiome-mediated brain alterations. Neurobiol Dis 2023; 179:106033. [PMID: 36758820 DOI: 10.1016/j.nbd.2023.106033] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Revised: 01/31/2023] [Accepted: 02/02/2023] [Indexed: 02/10/2023] Open
Abstract
Research in the last decade has unveiled a crucial role for the trillions of microorganisms that reside in the gut in influencing host neurodevelopment across the lifespan via the microbiota-gut-brain axis. Studies have linked alterations in the composition, complexity, and diversity of the gut microbiota to changes in behaviour including abnormal social interactions, cognitive deficits, and anxiety- and depressive-like phenotypes. Moreover, the microbiota has been linked with neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Interestingly, there appears to be specific brain regions governing the neurocircuitry driving higher cognitive function that are susceptible to influence from manipulations to the host microbiome. This review will aim to elucidate the region-specific effects mediated by the gut microbiota, with a focus on translational animal models and some existing human neuroimaging data. Compelling preclinical evidence suggests disruption to normal microbiota-gut-brain signalling can have detrimental effects on the prefrontal cortex, amygdala, hippocampus, hypothalamus, and striatum. Furthermore, human neuroimaging studies have unveiled a role for the microbiota in mediating functional connectivity and structure of specific brain regions that can be traced back to neurocognition and behavioural output. Understanding these microbiota-mediated changes will aid in identifying unique therapeutic targets for treating neurological disorders associated with these regions.
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Affiliation(s)
- Brendan L Sharvin
- APC Microbiome, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - Maria Rodriguez Aburto
- APC Microbiome, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
| | - John F Cryan
- APC Microbiome, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
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10
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Vuong HE. Intersections of the microbiome and early neurodevelopment. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2022; 167:1-23. [PMID: 36427952 DOI: 10.1016/bs.irn.2022.06.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Our resident microbes influence nearly all aspects of our biological systems. In particular, the maternal and early life microbiota is uniquely positioned to influence the development of the nervous system, and alterations to the gut microbiota, or dysbiosis, during this critical time in early life can have long-lasting negative effects on health. The question of how the maternal and early life microbiota shapes neurodevelopment is the topic of numerous investigations. Here, we discuss two possible, but not necessarily independent, hypotheses: (1) the maternal microbiota during pregnancy regulates the metabolites that are important for fetal development, (2) maternal microbiota seeded to offspring at birth and early postnatal days programs offspring immune and brain development, and regulates key molecules for postnatal brain development. In this chapter, we provide an overview of the impact of the microbiota on brain and behavior, introduce the maternal gut and vaginal microbiome during pregnancy, and discuss current understandings of microbiome in the context of developmental origins of health and disease. We consider novel translational insights that harness the multitude of microbes and microbial metabolites for prevention or treatment of neurological disorders.
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Affiliation(s)
- Helen E Vuong
- Department of Pediatrics, Division of Neonatology, University of Minnesota Twin Cities, Minneapolis, MN, United States.
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11
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Adams SH, Wright R, Piccolo BD, Moody B, Sikes J, Avaritt N, Chintapalli SV, Ou X. C-section increases cecal abundance of the archetypal bile acid and glucocorticoid modifying Lachnoclostridium [clostridium] scindens in mice. Physiol Rep 2022; 10:e15363. [PMID: 35778808 PMCID: PMC9249977 DOI: 10.14814/phy2.15363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 05/24/2022] [Accepted: 06/06/2022] [Indexed: 11/29/2022] Open
Abstract
In humans and animal models, Cesarean section (C‐section) has been associated with alterations in the taxonomic structure of the gut microbiome. These changes in microbiota populations are hypothesized to impact immune, metabolic, and behavioral/neurologic systems and others. It is not clear if birth mode inherently changes the microbiome, or if C‐section effects are context‐specific and involve interactions with environmental and other factors. To address this and control for potential confounders, cecal microbiota from ~3 week old mice born by C‐section (n = 16) versus natural birth (n = 23) were compared under matched conditions for housing, cross‐fostering, diet, sex, and genetic strain. A total of 601 unique species were detected across all samples. Alpha diversity richness (i.e., how many species within sample; Chao1) and evenness/dominance (i.e., Shannon, Simpson, Inverse Simpson) metrics revealed no significant differences by birth mode. Beta diversity (i.e., differences between samples), as estimated with Bray‐Curtis dissimilarities and Aitchison distances (using log[x + 1]‐transformed counts), was also not significantly different (Permutational Multivariate ANOVA [PERMANOVA]). Only the abundance of Lachnoclostridium [Clostridium] scindens was found to differ using a combination of statistical methods (ALDEx2, DESeq2), being significantly higher in C‐section mice. This microbe has been implicated in secondary bile acid production and regulation of glucocorticoid metabolism to androgens. From our results and the extant literature we conclude that C‐section does not inherently lead to large‐scale shifts in gut microbiota populations, but birth mode could modulate select bacteria in a context‐specific manner: For example, involving factors associated with pre‐, peri‐, and postpartum environments, diet or host genetics.
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Affiliation(s)
- Sean H Adams
- Department of Surgery, School of Medicine, University of California, Davis, California, USA.,Center for Alimentary and Metabolic Science, University of California, Davis, California, USA
| | - Rachel Wright
- Department of Surgery, School of Medicine, University of California, Davis, California, USA.,Center for Alimentary and Metabolic Science, University of California, Davis, California, USA
| | - Brian D Piccolo
- Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA.,Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Becky Moody
- Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA
| | - James Sikes
- Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA
| | - Nathan Avaritt
- Department of Biochemistry, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Sree V Chintapalli
- Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA.,Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Xiawei Ou
- Arkansas Children's Nutrition Center, Little Rock, Arkansas, USA.,Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.,Department of Radiology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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12
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Samuel TM, Thielecke F, Lavalle L, Chen C, Fogel P, Giuffrida F, Dubascoux S, Martínez-Costa C, Haaland K, Marchini G, Agosti M, Rakza T, Costeira MJ, Picaud JC, Billeaud C, Thakkar SK. Mode of Neonatal Delivery Influences the Nutrient Composition of Human Milk: Results From a Multicenter European Cohort of Lactating Women. Front Nutr 2022; 9:834394. [PMID: 35464009 PMCID: PMC9033294 DOI: 10.3389/fnut.2022.834394] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 02/18/2022] [Indexed: 12/03/2022] Open
Abstract
Background The effect of the mode of neonatal delivery (cesarean or vaginal) on the nutrient composition of human milk (HM) has rarely been studied. Given the increasing prevalence of cesarean section (C-section) globally, understanding the impact of C-section vs. vaginal delivery on the nutrient composition of HM is fundamental when HM is the preferred source of infant food during the first 4 postnatal months. Objective This study aimed to evaluate the association between mode of delivery and nutrient composition of HM in the first 4 months of life. Design Milk samples were obtained from 317 healthy lactating mothers as part of an exploratory analyses within a multicenter European longitudinal cohort (ATLAS cohort) to study the HM composition, and its potential association with the mode of delivery. We employed traditional mixed models to study individual nutrient associations adjusted for mother’s country, infant birth weight, parity, and gestational age, and complemented it, for the first time, with a multidimensional data analyses approach (non-negative tensor factorization, NTF) to examine holistically how patterns of multiple nutrients and changes over time are associated with the delivery mode. Results Over the first 4 months, nutrient profiles in the milk of mothers who delivered vaginally (n = 237) showed significantly higher levels of palmitoleic acid (16:1n-7), stearic acid (18:0), oleic acid (18:1n-9), arachidic acid (20:0), alpha-linolenic acid (18:3n-3), eicosapentaenoic acid (20:5n-3), docosahexenoic acid (22:6n-3), erucic acid (22:1n-9), monounsaturated fatty acids (MUFA)%, calcium, and phosphorus, whereas the ratios of arachidonic acid/docosahexaenoic acid (ARA/DHA) and n-6/n-3, as well as polyunsaturated fatty acids (PUFA)% were higher in milk from women who had C-sections, in the unadjusted analyses (p < 0.05 for all), but did not retain significance when adjusted for confounders in the mixed models. Using a complementary multidimension data analyses approach (NTF), we show few similar patterns wherein a group of mothers with a high density of C-sections showed increased values for PUFA%, n-6/n-3, and ARA/DHA ratios, but decreased values of MUFA%, 20:1n-9, iodine, and fucosyl-sialyl-lacto-N-tetraose 2 during the first 4 months of lactation. Conclusion Our data provide preliminary insights on differences in concentrations of several HM nutrients (predominantly fatty acids) among women who delivered via C-section. Although these effects tend to disappear after adjustment for confounders, given the similar patterns observed using two different data analytical approaches, these preliminary findings warrant further confirmation and additional insight on the biological and clinical effects related to such differences early in life.
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Affiliation(s)
- Tinu M. Samuel
- Nestlé Research, Société des Produits Nestlé S.A., Lausanne, Switzerland
| | - Frank Thielecke
- Department of Health Promotion, Swiss Distance University of Applied Sciences, Regensdorf, Brig, Switzerland
| | - Luca Lavalle
- Nestlé Research, Société des Produits Nestlé S.A., Lausanne, Switzerland
| | - Cheng Chen
- Nestlé Research, Société des Produits Nestlé S.A., Lausanne, Switzerland
| | | | | | - Stephane Dubascoux
- Nestlé Research, Société des Produits Nestlé S.A., Lausanne, Switzerland
| | | | | | | | | | - Thameur Rakza
- Centre d’Investigation Clinique de Lille, Hôpital Jeanne de Flandre, Lille, France
| | | | | | | | - Sagar K. Thakkar
- Nestlé Research, Société des Produits Nestlé S.A., Singapore, Singapore
- *Correspondence: Sagar K. Thakkar,
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13
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Wu M, Wang L, Liu Y, Bi J, Liu Q, Chen K, Li Y, Xia W, Xu S, Zhou A, Cao Z, Wang Y, Yang R. Association between early-term birth and delayed neurodevelopment at the age of 2 years: results from a cohort study in China. Eur J Pediatr 2021; 180:3509-3517. [PMID: 34137921 DOI: 10.1007/s00431-021-04152-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 06/04/2021] [Accepted: 06/08/2021] [Indexed: 10/21/2022]
Abstract
A growing body of evidence indicates that early-term births (37-38 weeks of gestational age) have an increased risk of short-term and long-term complications. Here, we sought to explore the association between early-term births and the risk of delayed neurodevelopment at age 2 years. Pregnant women and their live singleton birth were recruited from a single tertiary hospital between October 2013 and February 2017. Mental and Psychomotor Development Indexes (MDI and PDI) were assessed using the Bayley Scales of Infant Development (BSID). Delayed neurodevelopment was defined as scores of PDI or MDI less than -1SD relative to the mean score of the study population. In total, 1678 full-term infants and 727 early-term infants were assessed when they were 2 years old. After adjustment for potential confounders, early-term birth was related to 43% increased odds of neurodevelopmental delay in the PDI domain as compared with full-term birth (OR: 1.43; 95% CI: 1.12, 1.82). The observed associations were more prominent among those infants born by cesarean (OR: 1.44; 95% CI: 1.03, 2.00) and among males (OR: 1.66; 95% CI: 1.20, 2.28). No statistical difference in the MDI domain was found between early-term and full-term births.Conclusions: Our findings suggest that early-term birth was associated with increased odds of delayed neurodevelopment in the PDI domain as measured by BSID assessments at age 2 years. Health professionals should be aware of the influence of early-term birth on the risk of delayed neurodevelopment. What is Known: • Evidence indicates that early-term births have an increased risk of short-term and long-term complications. • The association between early-term births and delayed neurodevelopment at their early childhood has not been widely studied. What is New: • Early-term birth was associated with increased odds of delayed neurodevelopment in PDI domain as measured by BSID assessments at age 2 years. • The observed associations were more prominent among infants born by cesarean section and among male infants.
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Affiliation(s)
- Mingyang Wu
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Lulin Wang
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Yunyun Liu
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Jianing Bi
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Qing Liu
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Kai Chen
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Yuanyuan Li
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Wei Xia
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Shunqing Xu
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, 430030, Hubei, China
| | - Aifen Zhou
- Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, 100 Hong Kong Road, Wuhan, 430015, Hubei, China
| | - Zhongqiang Cao
- Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, 100 Hong Kong Road, Wuhan, 430015, Hubei, China
| | - Youjie Wang
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. .,Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, #13 Hangkong Road, Wuhan, 430030, Hubei, China.
| | - Rong Yang
- Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, 100 Hong Kong Road, Wuhan, 430015, Hubei, China.
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14
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Zavez A, Thurston SW, Rand MD, Mruzek DW, Love T, Smith T, Shamlaye CF, van Wijngaarden E. Delivery Mode and Child Development at 20 Months of Age and 7 Years of Age in the Republic of Seychelles. Matern Child Health J 2021; 25:1930-1938. [PMID: 34609706 PMCID: PMC8610017 DOI: 10.1007/s10995-021-03239-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/25/2021] [Indexed: 10/20/2022]
Abstract
OBJECTIVE To determine if cesarean delivery is adversely associated with child neurodevelopment as measured at 20 months and 7 years. METHODS In a prospective cohort study (n = 1328) in the Republic of Seychelles, we examined the association between mode of delivery and 22 measures of child neurodevelopment spanning multiple domains: cognition, executive and psychomotor function, language development, behavior, scholastic achievement, and social communication. Using multivariable linear regression, we evaluated the relationship between delivery mode (Cesarean/vaginal delivery) and each developmental outcome, while controlling for relevant covariates including child sex and age, maternal age, maternal IQ, whether both parents lived with the child, and Hollingshead socioeconomic status. RESULTS At 20 months, children born via cesarean delivery had slightly higher scores (β = 0.11, 95% confidence interval: 0.00, 0.21) on the Infant Behavior Questionnaire-Revised Positive Affectivity/Surgency subtest, a measure of infant temperament, as compared to vaginal delivery. Delivery mode was not associated with any of the 7-year developmental outcomes. CONCLUSIONS FOR PRACTICE Our study does not support the notion that cesarean delivery is associated with child neurodevelopmental outcomes.
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Affiliation(s)
- Alexis Zavez
- Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, 14642, USA.
| | - Sally W Thurston
- Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, 14642, USA
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, 14642, USA
| | - Matthew D Rand
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, 14642, USA
| | - Daniel W Mruzek
- Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, 14642, USA
| | - Tanzy Love
- Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, 14642, USA
| | - Tristram Smith
- Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, 14642, USA
| | | | - Edwin van Wijngaarden
- Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, 14642, USA
- Department of Public Health Sciences, University of Rochester Medical Center, Rochester, NY, 14642, USA
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15
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Williams LA, Sample J, McLaughlin CC, Mueller BA, Chow EJ, Carozza SE, Reynolds P, Spector LG. Sex differences in associations between birth characteristics and childhood cancers: a five-state registry-linkage study. Cancer Causes Control 2021; 32:1289-1298. [PMID: 34297242 DOI: 10.1007/s10552-021-01479-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 07/12/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND There is a well-recognized male excess in childhood cancer incidence; however, it is unclear whether there is etiologic heterogeneity by sex when defined by epidemiologic risk factors. METHODS Using a 5-state registry-linkage study (cases n = 16,411; controls n = 69,816), we estimated sex-stratified odds ratios (OR) and 95% confidence intervals (95% CI) between birth and demographic characteristics for 16 pediatric cancers. Evidence of statistical interaction (p-interaction < 0.01) by sex was evaluated for each characteristic in each cancer. RESULTS Males comprised > 50% of cases for all cancers, except Wilms tumor (49.6%). Sex interacted with a number of risk factors (all p-interaction < 0.01) including gestational age for ALL (female, 40 vs. 37-39 weeks OR: 0.84, 95% CI 0.73-0.97) and ependymoma (female, 40 vs. 37-39 OR: 1.78, 95% CI 1.14-2.79; female, ≥ 41 OR: 2.01. 95% CI 1.29-3.14), birth order for AML (female, ≥ 3rd vs. 1st OR: 1.39, 95% CI 1.01-1.92), maternal education for Hodgkin lymphoma (male, any college vs. < high school[HS] OR: 1.47, 95% CI 1.03-2.09) and Wilms tumor (female, any college vs. HS OR: 0.74, 95% CI 0.59-0.93), maternal race/ethnicity for neuroblastoma (male, black vs. white OR: 2.21, 95% CI 1.21-4.03; male, Hispanic vs. white OR: 1.86, 95% CI 1.26-2.75; female, Asian/Pacific Islander vs. white OR: 0.28, 95% CI 0.12-0.69), and paternal age (years) for hepatoblastoma in males (< 24 vs. 25-29 OR: 2.17, 95% CI 1.13-4.19; ≥ 35 vs. 25-29 OR: 2.44, 95% CI 1.28-4.64). CONCLUSIONS These findings suggest etiologic heterogeneity by sex for childhood cancers for gestational age, maternal education, and race/ethnicity and paternal age.
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Affiliation(s)
- Lindsay A Williams
- Division of Epidemiology & Clinical Research, Department of Pediatrics, University of Minnesota, MMC 715, 420 Delaware St. S.E, Minneapolis, MN, 55455, USA.
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
- Brain Tumor Program, University of Minnesota, Minneapolis, MN, USA.
| | - Jeannette Sample
- Division of Epidemiology & Clinical Research, Department of Pediatrics, University of Minnesota, MMC 715, 420 Delaware St. S.E, Minneapolis, MN, 55455, USA
| | | | - Beth A Mueller
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA
| | - Eric J Chow
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Susan E Carozza
- Department of Epidemiology and Biostatistics, School of Rural Public Health, Texas A&M Health Science Center, College Station, TX, USA
| | - Peggy Reynolds
- Department of Epidemiology and Biostatistics, University of California San Francisco, Berkeley, CA, USA
| | - Logan G Spector
- Division of Epidemiology & Clinical Research, Department of Pediatrics, University of Minnesota, MMC 715, 420 Delaware St. S.E, Minneapolis, MN, 55455, USA
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
- Brain Tumor Program, University of Minnesota, Minneapolis, MN, USA
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16
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Hamidzadeh A, Tavakol Z, Maleki M, Kolahdozan S, Khosravi A, Kiani M, Vaismoradi M. Effect of acupressure at the BL67 spot on the spontaneous rotation of fetus with breech presentation: A randomized controlled trial. Explore (NY) 2021; 18:567-572. [PMID: 34764014 DOI: 10.1016/j.explore.2021.10.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Revised: 10/02/2021] [Accepted: 10/16/2021] [Indexed: 11/25/2022]
Abstract
BACKGROUND Breech is a common fetal presentation in preterm pregnancies. This study aimed to investigate the effect of acupressure at the BL67 point on the spontaneous rotation of fetus with breech presentation. METHODS An unblind, two-armed randomized controlled trial was carried out from September 2017 to April 2020. Research participants were 138 pregnant women at 32 to 35 weeks of gestational age that had fetal breech presentation confirmed by ultrasound. They were randomly assigned into intervention and control groups (n=69 in each group). The intervention group received acupressure at the BL67 point on both feet for 10 minutes daily and for two consecutive weeks. The control group received routine care. Demographic and midwifery data questionnaires were used for data collection. RESULTS The spontaneous rotation of fetus with breech presentation into cephalic was observed in the majority of participants in the intervention group (82.6%) compared to the control group (17.4%) (p<0.001). Statistically significant differences in the fetal presentation at delivery was observed between the groups (84.1% cephalic vs. 18.8% breech, p<0.001). Regarding the type of delivery, cesarean section was reported mostly (85.5%) in the control group compared to the intervention group (21.7%) (p<0.001). However, the first- and fifth-minute Apgar scores of newborns had no statistically significant differences between the groups (p=0.773). CONCLUSION It is suggested to incorporate acupressure at the BL67 point into the care process for pregnant women to help with the reduction of the rate of cesarean section and avoid its related complications.
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Affiliation(s)
- Azam Hamidzadeh
- Student Research Committee, School of Nursing and Midwifery, Shahroud University of Medical Sciences, Shahroud, Iran.
| | - Zeinab Tavakol
- Community-Oriented Nursing Midwifery Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran.
| | - Maryam Maleki
- Pediatric and Neonatal Intensive Care Nursing Education Department, School of Nursing and Midwifery, Tehran University of Medical Sciences, Tehran, Iran.
| | - Sakineh Kolahdozan
- Sexual Health and Fertility Research Center, Shahroud University of Medical Sciences, Shahroud, Iran.
| | - Ahmad Khosravi
- Center for Health related Social and Behavioral Sciences Research, Shahroud University of Medical Sciences, Shahroud, Iran.
| | - Mahdieh Kiani
- School of Nursing and Midwifery, Shahroud University of Medical Sciences, Shahroud, Iran.
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17
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Kulaga SS, Miller CWT. Viral respiratory infections and psychosis: A review of the literature and the implications of COVID-19. Neurosci Biobehav Rev 2021; 127:520-530. [PMID: 33992695 PMCID: PMC9616688 DOI: 10.1016/j.neubiorev.2021.05.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 05/08/2021] [Accepted: 05/09/2021] [Indexed: 01/08/2023]
Abstract
The historical association between respiratory infections and neuropsychiatric symptoms dates back centuries, with more recent literature highlighting a link between viral infections and schizophrenia. Maternal influenza infection during pregnancy has been associated with the development of schizophrenia in offspring. Viral infections in neonates, children, and adolescents have also been associated with later development of schizophrenia. Neuroinvasive and/or systemic infections are thought to increase risk for psychopathology via inflammatory mechanisms, particularly when exposure occurs during critical neurodevelopmental windows. Several human coronaviruses (HCoVs) have been associated with psychotic disorders and increasing reports of the neuropsychiatric manifestations of COVID-19 suggest it has neuroinvasive properties similar to those of other HCoVs. These properties, in conjunction with its ability to generate a massive inflammatory response, suggest that COVID-19 may also contribute to future psychopathology. This review will summarize the psychopathogenic mechanisms of viral infections and discuss the neuroinvasive and inflammatory properties of COVID-19 that could contribute to the development of psychotic disorders, with a focus on in utero, neonatal, and childhood exposure.
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Affiliation(s)
- Stephanie S Kulaga
- University of Maryland School of Medicine, 701 W. Pratt St., 4th Floor, Baltimore, MD 21201, United States.
| | - Christopher W T Miller
- University of Maryland School of Medicine, 701 W. Pratt St., 4th Floor, Baltimore, MD 21201, United States
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18
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King J. Are there adverse outcomes for child health and development following caesarean section delivery? Can we justify using elective caesarean section to prevent obstetric pelvic floor damage? Int Urogynecol J 2021; 32:1963-1969. [PMID: 33877375 DOI: 10.1007/s00192-021-04781-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Accepted: 03/24/2021] [Indexed: 02/06/2023]
Abstract
INTRODUCTION AND HYPOTHESIS Elective pre-labour Caesarean section (CS) delivery is widely regarded as the panacea for all pelvic floor dysfunction despite substantial epidemiological evidence that it is only partially protective. To demand a CS is also considered a right for the well-counselled patient, even without an elevated risk of incontinence or prolapse. In recent years there has been increasing data on possible adverse health outcomes for children delivered by CS over those delivered vaginally. This includes respiratory illness, atopic conditions, obesity, diabetes and other severe auto-immune diseases. Concern has also been raised over possible impacts on cognitive and neuropsychological development in these children. Often the response has been to dismiss these outcomes as a result of the indication for the CS birth such as antenatal compromise or maternal disease. However the marked increase in non-medical Caesarean delivery throughout many regions of the world has allowed us to better distinguish these contributing factors. METHODS This narrative review looks at some of the more recent evidence on adverse health and developmental outcomes associated with CS, particularly pre-labour CS and the implications for the long term health of our society. RESULTS Epidemiological studies and animal research indicate an increased risk of negative impacts on child physical health and neuro-cognitive development aftercaesarean section delivery, particularly pre-labour Caesarean section, compared with vaginal delivery. This elevated risk persists after correction forobstetric and maternal factors. CONCLUSION Caesarean section delivery can result in adverse outcomes for infant, maternal and societal wellbeing. Elective Caesarean section, purely to potentially minimise pelvic floor dysfunction, cannot be justified.
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Affiliation(s)
- Jennifer King
- Pelvic Floor Unit, Westmead Hospital, Sydney, Australia.
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19
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Kenkel W. Birth signalling hormones and the developmental consequences of caesarean delivery. J Neuroendocrinol 2021; 33:e12912. [PMID: 33145818 PMCID: PMC10590550 DOI: 10.1111/jne.12912] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 10/05/2020] [Accepted: 10/06/2020] [Indexed: 12/12/2022]
Abstract
Rates of delivery by caesarean section (CS) are increasing around the globe and, although several epidemiological associations have already been observed between CS and health outcomes in later life, more are sure to be discovered as this practice continues to gain popularity. The components of vaginal delivery that protect offspring from the negative consequences of CS delivery in later life are currently unknown, although much attention to date has focused on differences in microbial colonisation. Here, we present the case that differing hormonal experiences at birth may also contribute to the neurodevelopmental consequences of CS delivery. Levels of each of the 'birth signalling hormones' (oxytocin, arginine vasopressin, epinephrine, norepinephrine and the glucocorticoids) are lower following CS compared to vaginal delivery, and there is substantial evidence for each that manipulations in early life results in long-term neurodevelopmental consequences. We draw from the research traditions of neuroendocrinology and developmental psychobiology to suggest that the perinatal period is a sensitive period, during which hormones achieve organisational effects. Furthermore, there is much to be learned from research on developmental programming by early-life stress that may inform research on CS, as a result of shared neuroendocrine mechanisms at work. We compare and contrast the effects of early-life stress with those of CS delivery and propose new avenues of research based on the links between the two bodies of literature. The research conducted to date suggests that the differences in hormone signalling seen in CS neonates may produce long-term neurodevelopmental consequences.
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Affiliation(s)
- William Kenkel
- Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, USA
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20
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Tremblay ME, Madore C, Bordeleau M, Tian L, Verkhratsky A. Neuropathobiology of COVID-19: The Role for Glia. Front Cell Neurosci 2020; 14:592214. [PMID: 33304243 PMCID: PMC7693550 DOI: 10.3389/fncel.2020.592214] [Citation(s) in RCA: 104] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Accepted: 10/07/2020] [Indexed: 12/18/2022] Open
Abstract
SARS-CoV-2, which causes the Coronavirus Disease 2019 (COVID-19) pandemic, has a brain neurotropism through binding to the receptor angiotensin-converting enzyme 2 expressed by neurones and glial cells, including astrocytes and microglia. Systemic infection which accompanies severe cases of COVID-19 also triggers substantial increase in circulating levels of chemokines and interleukins that compromise the blood-brain barrier, enter the brain parenchyma and affect its defensive systems, astrocytes and microglia. Brain areas devoid of a blood-brain barrier such as the circumventricular organs are particularly vulnerable to circulating inflammatory mediators. The performance of astrocytes and microglia, as well as of immune cells required for brain health, is considered critical in defining the neurological damage and neurological outcome of COVID-19. In this review, we discuss the neurotropism of SARS-CoV-2, the implication of neuroinflammation, adaptive and innate immunity, autoimmunity, as well as astrocytic and microglial immune and homeostatic functions in the neurological and psychiatric aspects of COVID-19. The consequences of SARS-CoV-2 infection during ageing, in the presence of systemic comorbidities, and for the exposed pregnant mother and foetus are also covered.
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Affiliation(s)
- Marie-Eve Tremblay
- Axe Neurosciences, Centre de Recherche du CHU de Québec, Université Laval, Québec City, QC, Canada
- Neurology and Neurosurgery Department, McGill University, Montréal, QC, Canada
- Department of Molecular Medicine, Université Laval, Québec City, QC, Canada
- Division of Medical Sciences, University of Victoria, Victoria, BC, Canada
- Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada
| | - Charlotte Madore
- Univ. Bordeaux, INRAE, Bordeaux INP, NutriNeuro, UMR 1286, Bordeaux, France
| | - Maude Bordeleau
- Axe Neurosciences, Centre de Recherche du CHU de Québec, Université Laval, Québec City, QC, Canada
- Neurology and Neurosurgery Department, McGill University, Montréal, QC, Canada
| | - Li Tian
- Department of Physiology, Faculty of Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
- Psychiatry Research Centre, Peking University Health Science Center, Beijing Huilongguan Hospital, Beijing, China
| | - Alexei Verkhratsky
- Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
- Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
- Department of Neurosciences, University of the Basque Country Universidad del País Vasco/Euskal Herriko Unibertsitatea, Leioa, Spain
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21
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Słabuszewska-Jóźwiak A, Szymański JK, Ciebiera M, Sarecka-Hujar B, Jakiel G. Pediatrics Consequences of Caesarean Section-A Systematic Review and Meta-Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E8031. [PMID: 33142727 PMCID: PMC7662709 DOI: 10.3390/ijerph17218031] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 10/28/2020] [Accepted: 10/29/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Cesarean section is a surgical procedure, which is the most frequently performed in gynecology and obstetrics. It is commonly believed that an operative delivery is a less painful and safer mode of delivery, which translates into an increasing number of the procedures performed without medical indications. The maternal sequelae of cesarean sections are well elucidated and widely discussed in the literature, while long-term neonatal consequences still remain the issue of research and scientific dispute. The aim of the present paper was to perform a systematic review of current literature regarding pediatrics consequences of cesarean section. METHODS We reviewed available data from PubMed, Science Direct as well as Google Scholar bases concerning early and long-term neonatal sequelae of operative deliveries. The following key words were used: "cesarean section", "caesarean section", "neonatal outcomes", "respiratory disorders", "asthma", "obesity", "overweight", and "neurological disorders". A total of 1636 papers were retrieved out of which 27 were selected for the final systematic review whereas 16 articles provided data for meta-analysis. Statistical analyses were performed using RevMan 5.4. To determine the strength of association between the caesarean section and respiratory tract infections, asthma, diabetes type 1 as well as obesity the pooled odds ratios (OR) with the 95% confidence intervals (CI) were calculated. RESULTS Conducted meta-analyses revealed that caesarean section is a risk factor for respiratory tract infections (pooled OR = 1.30 95%CI 1.06-1.60, p = 0.001), asthma (pooled OR = 1.23 95%CI 1.14-1.33, p < 0.00001) as well as obesity (pooled OR = 1.35 95%CI 1.29-1.41, p < 0.00001) in offspring. CONCLUSIONS The results of the studies included indicated that children delivered by cesarean section more commonly developed respiratory tract infections, obesity and the manifestations of asthma than children delivered vaginally. The risk of developing diabetes mellitus type 1 or neurological disorders in offspring after caesarean section is still under discussion.
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Affiliation(s)
- Aneta Słabuszewska-Jóźwiak
- First Department of Obstetrics and Gynaecology, Centre of Postgraduate Medical Education, Żelazna 90 Street, 01-004 Warsaw, Poland; (J.K.S.); (G.J.)
| | - Jacek Krzysztof Szymański
- First Department of Obstetrics and Gynaecology, Centre of Postgraduate Medical Education, Żelazna 90 Street, 01-004 Warsaw, Poland; (J.K.S.); (G.J.)
| | - Michał Ciebiera
- Second Department of Obstetrics and Gynaecology, Centre of Postgraduate Medical Education, Cegłowska 80 Street, 01-809 Warsaw, Poland;
| | - Beata Sarecka-Hujar
- Department of Basic Biomedical Science, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Kasztanowa 3 Street, 41-200 Sosnowiec, Poland;
| | - Grzegorz Jakiel
- First Department of Obstetrics and Gynaecology, Centre of Postgraduate Medical Education, Żelazna 90 Street, 01-004 Warsaw, Poland; (J.K.S.); (G.J.)
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22
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Sadowska M, Sarecka-Hujar B, Kopyta I. Evaluation of Risk Factors for Epilepsy in Pediatric Patients with Cerebral Palsy. Brain Sci 2020; 10:brainsci10080481. [PMID: 32722475 PMCID: PMC7463548 DOI: 10.3390/brainsci10080481] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 07/18/2020] [Accepted: 07/23/2020] [Indexed: 01/14/2023] Open
Abstract
Cerebral palsy (CP) is a set of etiologically diverse symptoms that change with the child's age. It is one of the most frequent causes of motor disability in children. CP occurs at a frequency of 1.5 to 3.0 per 1000 live-born children. CP often coexists with epilepsy, which is drug-resistant in a high number of cases. The aim of the present study was to analyze the associations between preconception, prenatal, perinatal, neonatal, and infancy risk factors for epilepsy in a group of pediatric patients with CP. We retrospectively analyzed 181 children with CP (aged 4-17 years at diagnosis), hospitalized at the Department of Pediatrics and Developmental Age Neurology in Katowice in the years 2008-2016. Division into particular types of CP was based on Ingram's classification. Data were analyzed using STATISTICA 13.0 (STATSOFT; Statistica, Tulsa, OK, USA). Epilepsy was diagnosed in 102 children (56.35%), of whom 44 (43%) had drug-resistant epilepsy; only in 15 cases (14.71%) was epilepsy susceptible to treatment. The incidence of epilepsy varied between the types of CP. It occurred significantly more often in children with tetraplegia (75%), ataxic form (83%), and mixed form (80%) in comparison to diplegia (32%) and hemiplegia (38%). Maternal hypertension was found to be a risk factor for epilepsy in CP patients (OR = 12.46, p < 0.001) as well as for drug-resistant epilepsy (the odds ratio (OR) = 9.86, p = 0.040). Delivery by cesarean section increased the risk of epilepsy in the CP patients over two-fold (OR = 2.17, p = 0.012). We observed also that neonatal convulsions significantly increased the risk for epilepsy (OR = 3.04, p = 0.011) as well as drug-resistant epilepsy (OR = 4.02, p = 0.002). In conclusion, maternal hypertension, neonatal convulsions, and delivery by cesarean section were the most important factors increasing the risk of epilepsy as well as drug-resistant epilepsy in the analyzed group of patients with CP.
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Affiliation(s)
- Małgorzata Sadowska
- Department of Pediatrics and Developmental Age Neurology, Upper Silesian Center for Child’s Health, 40-752 Katowice, Poland;
| | - Beata Sarecka-Hujar
- Department of Basic Biomedical Science, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland
- Correspondence: or ; Tel.: +48-322-699-830
| | - Ilona Kopyta
- Department of Pediatric Neurology, School of Medicine in Katowice, Medical University of Silesia in Katowice, 40-752 Katowice, Poland;
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23
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Martynyuk AE, Ju LS, Morey TE, Zhang JQ. Neuroendocrine, epigenetic, and intergenerational effects of general anesthetics. World J Psychiatry 2020; 10:81-94. [PMID: 32477904 PMCID: PMC7243620 DOI: 10.5498/wjp.v10.i5.81] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 03/18/2020] [Accepted: 03/26/2020] [Indexed: 02/05/2023] Open
Abstract
The progress of modern medicine would be impossible without the use of general anesthetics (GAs). Despite advancements in refining anesthesia approaches, the effects of GAs are not fully reversible upon GA withdrawal. Neurocognitive deficiencies attributed to GA exposure may persist in neonates or endure for weeks to years in the elderly. Human studies on the mechanisms of the long-term adverse effects of GAs are needed to improve the safety of general anesthesia but they are hampered not only by ethical limitations specific to human research, but also by a lack of specific biological markers that can be used in human studies to safely and objectively study such effects. The latter can primarily be attributed to an insufficient understanding of the full range of the biological effects induced by GAs and the molecular mechanisms mediating such effects even in rodents, which are far more extensively studied than any other species. Our most recent experimental findings in rodents suggest that GAs may adversely affect many more people than is currently anticipated. Specifically, we have shown that anesthesia with the commonly used GA sevoflurane induces in exposed animals not only neuroendocrine abnormalities (somatic effects), but also epigenetic reprogramming of germ cells (germ cell effects). The latter may pass the neurobehavioral effects of parental sevoflurane exposure to the offspring, who may be affected even at levels of anesthesia that are not harmful to the exposed parents. The large number of patients who require general anesthesia, the even larger number of their future unexposed offspring whose health may be affected, and a growing number of neurodevelopmental disorders of unknown etiology underscore the translational importance of investigating the intergenerational effects of GAs. In this mini review, we discuss emerging experimental findings on neuroendocrine, epigenetic, and intergenerational effects of GAs.
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Affiliation(s)
- Anatoly E Martynyuk
- Department of Anesthesiology and the McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Ling-Sha Ju
- Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Timothy E Morey
- Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Jia-Qiang Zhang
- Department of Anesthesiology and Perioperative Medicine, Henan Provincial People’s Hospital, People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
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