Nutrition prénatale et prénatale et troubles neuro-développementaux: revue systématique et méta-analyse

Aperçu: G.M.

La nutrition avant la conception et prénatale est essentielle au développement du cerveau fœtal. Cependant, ses associations avec les troubles neurodéveloppementaux de la progéniture ne sont pas bien comprises. 

Cette étude vise à examiner systématiquement les associations entre la préconception et la nutrition prénatale et le risque de troubles neurodéveloppementaux chez les enfants. 

Nous avons cherché PubMed et Embase des articles publiés jusqu'en mars 2019. Les expositions nutritionnelles comprenaient l'apport ou l'état de nutriments, l'apport alimentaire ou les habitudes alimentaires. Les résultats neurodéveloppementaux comprenaient les "troubles du spectre de l'autisme" (TSA), le trouble du déficit de l'attention / hyperactivité (TDAH) et les déficiences intellectuelles. 

Un total de 2169 articles ont été examinés, et 20 articles sur les TSA et 17 sur le TDAH ont finalement été examinés. 

Nous avons trouvé une association inverse globale entre la supplémentation maternelle en acide folique ou en multivitamines et le risque de TSA des enfants; méta-analyse comprenant six études de cohorte prospectives estimées à un RR de TSA de 0,64 (IC à 95%: 0,46, 0,90). 

Les données sur les associations entre d'autres facteurs alimentaires et les TSA, le THADA et les résultats connexes n'étaient pas concluantes et mériteraient d'être explorées ultérieurement. 

Les futures études devraient intégrer des méthodes complètes et plus objectives pour quantifier les expositions nutritionnelles et explorer un autre type d’étude tel que la randomisation mendélienne afin d’évaluer les effets causals potentiels.

Nutrients. 2019 Jul 17;11(7). pii: E1628. doi: 10.3390/nu11071628.

Preconception and Prenatal Nutrition and Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis

Li M¹, Francis E¹, Hinkle SN¹, Ajjarapu AS¹, Zhang C².

Author information

1

Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20817, USA.

2

Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20817, USA. zhangcu@mail.nih.gov.

Abstract

Preconception and prenatal nutrition is critical for fetal brain development. However, its associations with offspring neurodevelopmental disorders are not well understood. This study aims to systematically review the associations of preconception and prenatal nutrition with offspring risk of neurodevelopmental disorders. We searched the PubMed and Embase for articles published through March 2019. Nutritional exposures included nutrient intake or status, food intake, or dietary patterns. Neurodevelopmental outcomes included autism spectrum disorders (ASD), attention deficit disorder-hyperactivity (ADHD) and intellectual disabilities. A total of 2169 articles were screened, and 20 articles on ASD and 17 on ADHD were eventually reviewed. We found an overall inverse association between maternal folic acid or multivitamin supplementation and children's risk of ASD; a meta-analysis including six prospective cohort studies estimated an RR of ASD of 0.64 (95% CI: 0.46, 0.90). Data on associations of other dietary factors and ASD, ADHD and related outcomes were inconclusive and warrant future investigation. Future studies should integrate comprehensive and more objective methods to quantify the nutritional exposures and explore alternative study design such as Mendelian randomization to evaluate potential causal effects.

PMID: 31319515

DOI: 10.3390/nu11071628

Infection et fièvre pendant la grossesse et les "troubles du spectre de l'autisme": Résultats de l’étude visant à explorer le développement précoce

Aperçu: G.M.

L'infection maternelle et la fièvre pendant la grossesse ont été impliquées dans l'étiologie des "troubles du spectre de l'autisme" (TSA); Cependant, les études n'ont pas été en mesure de séparer les effets de la fièvre elle-même de l'impact d'un organisme infectieux spécifique sur le cerveau en développement. 

Nous avons utilisé les données de l’étude SEED (Study to Explore Early Development), une étude de cas-témoins menée auprès d’enfants de 2 à 5 ans nés entre 2003 et 2006 aux États-Unis, afin d’explorer un lien possible entre infection fébrile et fièvre maternelle grossesse et risque de TSA et d’autres troubles du développement (DD). 

Trois groupes d'enfants ont été inclus: les enfants avec un diagnostic de TSA (N = 606) et les enfants avec DD (N = 856), identifiés par des sources cliniques et éducatives, et les enfants de la population en général (N = 796), échantillonnés au hasard à partir des registres de naissance de l'État. .

Les informations sur l'infection et la fièvre pendant la grossesse ont été obtenues lors d'un entretien téléphonique avec la mère peu de temps après l'inscription à l'étude et des dossiers médicaux maternels prénatals et d'accouchement. Le statut de TSA et de DD a été déterminé par une évaluation développementale standardisée en personne de l'enfant âgé de 3 à 5 ans. Après ajustement pour tenir compte des covariables, l’infection maternelle à n’importe quel moment de la grossesse n’a pas été associée aux TSA ni aux DD.

Cependant, l’infection du deuxième trimestre accompagnée de fièvre a augmenté le risque de développer un TSA environ deux fois plus (AOR = 2,19, intervalle de confiance à 95%: 1,14-4,23). 

Ces résultats d'association entre une infection maternelle avec fièvre au deuxième trimestre et un risque accru de TSA chez la progéniture suggèrent que la réponse inflammatoire à l'agent infectieux pourrait être pertinente sur le plan étiologique. Autisme Res2019. © 2019 Société internationale de recherche sur l'autisme, Wiley Periodicals, Inc.

Autism Res. 2019 Jul 17. doi: 10.1002/aur.2175.

Infection and Fever in Pregnancy and Autism Spectrum Disorders: Findings from the Study to Explore Early Development

Croen LA¹, Qian Y¹, Ashwood P², Zerbo O¹, Schendel D^3,4, Pinto-Martin J⁵, Daniele Fallin M⁶, Levy S⁷, Schieve LA⁸, Yeargin-Allsopp M⁸, Sabourin KR⁹, Ames JL¹.

Author information

1

Division of Research, Kaiser Permanente, Oakland, California.

2

Department of Medical Microbiology and Immunology, University of California, Davis, California.

3

Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH; National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.

4

Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.

5

Department of Biobehavioral Health Sciences, Philadelphia, Pennsylvania, USA.

6

Department of Mental Health, Baltimore, Maryland, USA.

7

Department of Developmental and Behavioral Pediatrics, Philadelphia, Pennsylvania, USA.

8

National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia.

9

Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

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 Res2019. © 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.

© 2019 International Society for Autism Research, Wiley Periodicals, Inc.

PMID:31317667

DOI:10.1002/aur.2175

Exposition prénatale à l'alcool en relation avec le trouble du spectre de l'autisme: résultats de l'étude pour explorer le développement précoce (SEED).

Aperçu: G.M.

L'exposition prénatale à l'alcool peut affecter le développement neurologique, mais peu d'études ont examiné les associations avec le trouble du spectre de l'autisme (TSA).

Les chercheurs ont évalué l'association entre la consommation d'alcool maternelle et les TSA avec  l'Etude pour Explorer le Développement Précoce, une étude cas-contrôle multi-sites sur les enfants nés entre septembre 2003 et août 2006 aux États-Unis. 

Les mères d'enfants dans la population générale (POP) étaient plus susceptibles de signaler une consommation d'alcool prénatal que les mères d'enfants avec un diagnostic de TSA ou de retard de développement (DD). Au cours du trimestre, 21,2% des mères d'enfants POP ont déclaré une consommation d'alcool comparativement à 18,1% et 18,2% des mères d'enfants avec TSA ou DD, respectivement. Au cours de la préconception et du premier mois de grossesse, une à deux boissons en moyenne par semaine était inversement associée au risque de TSA. 

Ces résultats ne supportent pas une association négative entre l'exposition à l'alcool à faible niveau et la TSA, bien que ces résultats soient basés sur une consommation d'alcool rétrospective autodéclarée. Un mauvais classement ou une mauvaise classification de l'exposition peut expliquer les associations inverses avec une ou deux boissons par semaine.  

Les femmes enceintes ou potentiellement enceintes devraient continuer à suivre les recommandations pour éviter la consommation d'alcool en raison d'autres effets connus sur la santé du nourrisson et le développement neurologique. 

Paediatr Perinat Epidemiol. 2017 Sep 7. doi: 10.1111/ppe.12404.

Prenatal Alcohol Exposure in Relation to Autism Spectrum Disorder: Findings from the Study to Explore Early Development (SEED)

Singer AB¹, Aylsworth AS², Cordero C¹, Croen LA³, DiGuiseppi C⁴, Fallin MD^5,6,7, Herring AH⁸, Hooper SR⁹, Pretzel RE¹⁰, Schieve LA¹¹, Windham GC¹², Daniels JL¹.

Author information

1

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC.

2

Departments of Pediatrics and Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC.

3

Division of Research, Kaiser Permanente Northern California, Oakland, CA.

4

Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO.

5

Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.

6

Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.

7

The Wendy Klag Center for Autism and Developmental Disabilities, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD.

8

Department of Biostatistics and Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC.

9

Department of Allied Health Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC.

10

Carolina Institute for Developmental Disabilities (CIDD), University of North Carolina at Chapel Hill, Chapel Hill, NC.

11

National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA.

12

Division of Environmental and Occupational Disease Control, CA Department of Public Health, Oakland, CA.

Abstract

BACKGROUND:

Prenatal alcohol exposure can affect neurodevelopment, but few studies have examined associations with autism spectrum disorder (ASD).

METHODS:

We assessed the association between maternal alcohol use and ASD in the Study to Explore Early Development, a multi-site case-control study of children born between September 2003 and August 2006 in the US Regression analyses included 684 children with research clinician-confirmed ASD, 869 children with non-ASD developmental delays or disorders (DDs), and 962 controls ascertained from the general population (POP). Maternal alcohol exposure during each month from 3 months prior to conception until delivery was assessed by self-report.

RESULTS:

Mothers of POP children were more likely to report any prenatal alcohol use than mothers of children with ASD or DD. In trimester one, 21.2% of mothers of POP children reported alcohol use compared with 18.1% and 18.2% of mothers of children with ASD or DD, respectively (adjusted OR for ASD vs. POP 0.8, 95% confidence interval 0.6, 1.1). During preconception and the first month of pregnancy, one to two drinks on average per week was inversely associated with ASD risk.

CONCLUSIONS:

These results do not support an adverse association between low-level alcohol exposure and ASD, although these findings were based on retrospective self-reported alcohol use. Unmeasured confounding or exposure misclassification may explain inverse associations with one to two drinks per week. Pregnant or potentially pregnant women should continue to follow recommendations to avoid alcohol use because of other known effects on infant health and neurodevelopment.

© 2017 John Wiley & Sons Ltd.

PMID:28881390

DOI:10.1111/ppe.12404

Fièvre prénatale et risque d'autisme

Aperçu: G.M.

Certaines études suggèrent que l'infection prénatale augmente le risque de "troubles du spectre de l'autisme" (TSA). Cette étude a été entreprise dans une cohorte prospective en Norvège pour examiner si nous pouvions trouver des preuves pour soutenir une association de l'apparition prénatale de la fièvre, une manifestation commune d'infection, avec un risque de TSA. Des questionnaires prospectifs ont fourni des données sur l'exposition maternelle.

Le risque a augmenté nettement avec l'exposition à trois épisodes de fièvre ou plus après 12 semaines de gestation.  

Le risque de TSA semble augmenter avec la fièvre maternelle, en particulier au deuxième trimestre.  

Le risque augmente proportionnellement de degré avec une exposition à de multiples fièvres après une grossesse de 12 semaines.  

Ces résultats confortent le rôle de l'infection maternelle gestationnelle et des réponses immunitaires innées à une infection dans la pathogenèse d'au moins certains cas de TSA. 

Mol Psychiatry. 2017 Jun 13. doi: 10.1038/mp.2017.119.

Prenatal fever and autism risk

Hornig M^1,2, Bresnahan MA^2,3, Che X¹, Schultz AF¹, Ukaigwe JE¹, Eddy ML¹, Hirtz D⁴, Gunnes N⁵, Lie KK⁵, Magnus P⁵, Mjaaland S⁵, Reichborn-Kjennerud T^5,6, Schjølberg S⁵, Øyen AS^5,7, Levin B⁸, Susser ES^2,3, Stoltenberg C^5,9, Lipkin WI^1,2,10.

Author information

1

Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.

2

Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.

3

New York State Psychiatric Institute, New York, NY, USA.

4

National Institute of Neurological Disorders and Stroke, National Institutes of Health, Rockville, MD, USA.

5

Norwegian Institute of Public Health, Oslo, Norway.

6

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

7

Lovisenberg Diakonale Sykehus, Nic Waals Institutt, Oslo, Norway.

8

Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.

9

Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.

10

Departments of Pathology and Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA.

Abstract

Some studies suggest that prenatal infection increases risk of autism spectrum disorders (ASDs). This study was undertaken in a prospective cohort in Norway to examine whether we could find evidence to support an association of the prenatal occurrence of fever, a common manifestation of infection, with ASD risk. Prospective questionnaires provided maternal exposure data; case status was established from clinical assessments and registry linkages. In a large, prospectively ascertained cohort of pregnant mothers and their offspring, we examined infants born ⩾32 weeks for associations between fever exposure in each trimester and ASD risk using logistic regression. Maternal exposure to second-trimester fever was associated with increased ASD risk, adjusting for presence of fever in other trimesters and confounders (adjusted odds ratio (aOR), 1.40; 95% confidence interval, 1.09-1.79), with a similar, but nonsignificant, point estimate in the first trimester. Risk increased markedly with exposure to three or more fever episodes after 12 weeks' gestation (aOR, 3.12; 1.28-7.63). ASD risk appears to increase with maternal fever, particularly in the second trimester. Risk magnified dose dependently with exposure to multiple fevers after 12 weeks' gestation. Our findings support a role for gestational maternal infection and innate immune responses to infection in the pathogenesis of at least some cases of ASD.Molecular Psychiatry advance online publication, 13 June 2017; doi:10.1038/mp.2017.119.

PMID:28607458

DOI:10.1038/mp.2017.119

Concentration urinaire des métabolites des insecticides organophosphorés pendant la grossesse et comportement interpersonnel, communication, répétitif et stéréotypé des enfants à l'âge de 8 ans: l'étude à domicile

Aperçu: G.M.

L'exposition prénatale aux insecticides organophosphorés peut être associée à des troubles du spectre de l'autisme et à des comportements connexes. Cette association peut être modifiée par des polymorphismes nucléotidiques simples dans l'enzyme de la paraoxonase (PON1).

 Parmi 224 femmes enceintes, les chercheurs ont quantifié les concentrations de six métabolites non spécifiques du phosphate de dialkyle (DAP) des insecticides organophosphorés dans deux échantillons d'urine recueillis à ~ 16 et ~ 26 semaines de gestation.  

Lorsque les enfants avaient huit ans, les chercheurs leur ont fait passé l'échelle de réceptivité sociale (SRS), une mesure continue de diverses dimensions du comportement interpersonnel, de la communication et des comportements répétitifs / stéréotypés. Ils ont ensuite estimé l'association entre une augmentation de 10 fois de la somme de six concentrations de DAP (ΣDAP) et les scores de SRS. ILs ont enfin examiné si les génotypes enfants PON1192 et PON1-108 ont modifié cette association.

Après l'ajustement covariable, les concentrations de ΣDAP n'ont pas été associées aux scores SRS  

Environ Res. 2017 May 10;157:9-16. doi: 10.1016/j.envres.2017.05.008.

Urinary organophosphate insecticide metabolite concentrations during pregnancy and children's interpersonal, communication, repetitive, and stereotypic behaviors at 8 years of age: The home study

Millenson ME¹, Braun JM², Calafat AM³, Barr DB⁴, Huang YT⁵, Chen A⁶, Lanphear BP⁷, Yolton K⁸.

Author information

1

Department of Epidemiology, Brown University, Providence, RI 02912, USA.

2

Department of Epidemiology, Brown University, Providence, RI 02912, USA. Electronic address: joseph_braun_1@brown.edu.

3

Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.

4

Department of Environmental Health, Emory University, Atlanta, GA, USA.

5

Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.

6

Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.

7

Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.

8

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Abstract

BACKGROUND:

Prenatal exposure to organophosphate insecticides may be associated with autism spectrum disorders and related behaviors. This association may be modified by single nucleotide polymorphisms in the paraoxonase (PON1) enzyme.

OBJECTIVE:

We examined the relationship of prenatal organophosphate insecticide biomarkers with reciprocal social, repetitive, and stereotypic behaviors in 8-year old children, and modification of this relationship by child PON1 polymorphisms.

METHODS:

Among 224 pregnant women, we quantified concentrations of six nonspecific dialkyl phosphate (DAP) metabolites of organophosphate insecticides in two urine samples collected at ~16 and ~26 weeks gestation. When children were eight years old, we administered the Social Responsiveness Scale (SRS), a continuous measure of various dimensions of interpersonal behavior, communication, and repetitive/stereotypic behaviors. We estimated the association between a 10-fold increase in the sum of six DAP concentrations (ΣDAP) and SRS scores. We examined whether child PON1₁₉₂ and PON1_-108 genotypes modified this association.

RESULTS:

After covariate adjustment, ΣDAP concentrations were not associated with SRS scores [β=-1.2; 95% confidence interval (CI): -4.0, 1.6]. Among children with the PON1_-108TT genotype, ΣDAP concentrations were associated with 2.5-point higher (95% CI: -4.9, 9.8) SRS scores; however, the association was not different from the 1.8-point decrease (95% CI: -5.8, 2.2) among children with PON1_-108CT/CC genotypes (ΣDAP × PON1_-108 p-value =0.54). The association between ΣDAP concentrations and SRS scores was not modified by PON1₁₉₂ (ΣDAP × PON1₁₉₂ p-value =0.89).

CONCLUSIONS:

In this cohort, prenatal urinary DAP concentrations were not associated with children's social behaviors; these associations were not modified by child PON1 genotype.

Copyright © 2017 Elsevier Inc. All rights reserved.

PMID: 28501654

DOI: 10.1016/j.envres.2017.05.008

Le chlorpyrifos prénatal conduit à des déficits autistiques chez les souris C57Bl6 / J

Aperçu: G.M.

Nos données indiquent que l'exposition gestationnelle au CPF (chlorpyrifos) a des effets délétères à long terme sur le comportement social et limite l'exploration d'objets nouveaux

Cliquez ICI pour accéder à l’intégralité de l'article en anglais

Environ Health. 2017 May 2;16(1):43. doi: 10.1186/s12940-017-0251-3.

Prenatal chlorpyrifos leads to autism-like deficits in C57Bl6/J mice

Lan A^1,2, Kalimian M¹, Amram B¹, Kofman O^3,4.

Author information

1

Department of Psychology, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva, 84105, Israel.

2

Zlotowski Centre for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

3

Department of Psychology, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva, 84105, Israel. kofman@bgu.ac.il

4

Zlotowski Centre for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel. kofman@bgu.ac.il.

Abstract

BACKGROUND:

Children are at daily risk for exposure to organophosphate insecticides, of which the most common is chlorpyrifos (CPF). Exposure of pregnant women to CPF was linked to decreased birth weight, abnormal reflexes, reduction in IQ, as well as increased maternal reports of signs of pervasive developmental disorder. The aim of current study was to examine the long term effects of prenatal exposure to CPF in C57BL/6 J (B6) mice with specific focus on social and repetitive behavior.

METHODS:

B6 female mice were treated with vehicle, 2.5 mg/kg CPF or 5 mg/kg of CPF on gestational days 12-15 by oral gavage. On postnatal days (PND's) 6-12 early development and neuromotor ability were assessed by measuring 3 neonatal reflexes in the offspring. In adulthood, PND 90, social behavior was investigated using the social preference, social novelty and social conditioned place preference tasks. Object recognition and restricted interest, measured by the repetitive novel object contact task (RNOC), were also assessed on PN D 90. In order to rule out the possibility that CPF administration induced alterations in maternal care, the dams' behavior was evaluated via the maternal retrieval task.

RESULTS:

CPF treatment resulted in delayed development of neonatal reflexes on PND's 6-12. On PND 90, mice treated prenatally with the 5.0 mg/kg dose exhibited reduced preference towards an unfamiliar conspecific in the social preference test and reduced social conditioned place preference. In the RNOC task, mice exposed prenatally to 2.5 mg/kg dose of CPF showed enhanced restricted interest. CPF administration did not impair dams' behavior and did not cause memory or recognition deficit as was observed in the object recognition task.

CONCLUSIONS:

Our data indicate that gestational exposure to CPF has long-term deleterious effects on social behavior and limits exploration of novel objects.

PMID: 28464876

PMCID: PMC5414283

DOI: 10.1186/s12940-017-0251-3

L'exposition prénatale aux agonistes β2-adrénergiques et le risque de trouble du spectre de l'autisme chez les descendants

Aperçu: G.M.
L'étude a à examiner le risque de troubles du spectre de l'autisme (TSA) dans la progéniture qui ont été exposés à une utilisation maternelle de l'agoniste β2-adrénergique (β2AA) pendant la grossesse.
Les résultats montrent un risque accru de TSA chez les enfants exposés (IRR = 1.28, 1.11-1.47), en particulier pour ceux qui ont été exposés au cours de la deuxième période (IRR = 1.38, 1.14-1.67). Toutefois, lorsqu'on a prolongé la durée du temps d'exposition à 1 an avant la grossesse, l'étude montre une association similaire chez les enfants nés de femmes qui ont reçu un traitement β2AA pendant la grossesse (IRR = 1.33, 1.11-1.59) à celui des enfants nés chez les femmes qui ont reçu un traitement β2AA, 1 an avant la grossesse
Notre constat a suggéré que les enfants nés de femmes qui ont utilisé β2AA pendant la grossesse ont un risque accru de TSA plus tard, ce qui est plus susceptible d'être dû aux maladies maternelles sous-jacentes que l'exposition à β2AA elle-même.

Pharmacoepidemiol Drug Saf. 2017 Apr 19. doi: 10.1002/pds.4214.

Prenatal exposure to β2-adrenoreceptor agonists and the risk of autism spectrum disorders in offspring

Su X¹, Yuan W², Chen J², Miao M², Olsen J³, Pedersen LH⁴, Liang H², Li J³.

Author information

1

Department of Women and Children's Health Care, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.

2

Key Lab of Reproductive Regulation of NPFPC, SIPPR; IRD, Fudan University, Shanghai, China.

3

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.

4

Department of Clinical Medicine, Obstetrics and Gynecology, Aarhus University, Aarhus, Denmark.

Abstract

PURPOSE:

We aimed to examine the risk of autism spectrum disorders (ASDs) in the offspring who were exposed to maternal use of β2-adrenoreceptor agonist (β2AA) during pregnancy.

METHODS:

This is a population-based cohort study including all live singleton births in Denmark from 1 January 1997 to 31 December 2008. Children born to mothers who used β2AA during pregnancy were categorized as exposed, and all other children were included in the unexposed group. Cases of ASDs were identified from the Danish Psychiatric Central Register and the Danish Patient Register. Incidence rate ratio (IRR) and 95% confidence interval were estimated by Poisson regression models.

RESULTS:

Among 751 888 children in the cohort, 9098 (1.21%) received a diagnosis of ASDs. We observed an increased risk of ASDs in the exposed children (IRR = 1.28, 1.11-1.47), especially for those who were exposed during the second trimester period (IRR = 1.38, 1.14-1.67). However, when extending the exposure time window to 1 year prior to pregnancy, we observed a similar association in children born to women who received β2AA treatment during pregnancy (IRR = 1.33, 1.11-1.59) to that in children born to women who received β2AA treatment 1 year prior to pregnancy (IRR = 1.35, 1.17-1.56).

CONCLUSION:

Our finding suggested that children born to women who used β2AA during pregnancy have an increased risk of ASDs in later life, which is more likely due to underlying maternal diseases rather than the exposure to β2AA itself. However, further study, which would better differentiate the effects between indication and medicine, is needed to corroborate the finding. Copyright © 2017 John Wiley & Sons, Ltd.

Copyright © 2017 John Wiley & Sons, Ltd.

PMID: 28422339

DOI: 10.1002/pds.4214

Risque de troubles du spectre de l'autisme selon la période d'exposition aux antidépresseurs prénatals: un examen systématique et une méta-analyse

Aperçu: G.M.

Il existe une association significative entre l'augmentation du risque de TSA et l'utilisation maternelle des antidépresseurs pendant la grossesse; Cependant, il semble être plus cohérent pendant la période de préconception que pendant chaque trimestre. Les troubles psychiatriques maternels dans le traitement avant la grossesse plutôt que l'exposition prénatale aux antidépresseurs pourraient avoir un rôle majeur dans le risque de TSA.

JAMA Pediatr. 2017 Apr 17. doi: 10.1001/jamapediatrics.2017.0124.

Risk for Autism Spectrum Disorders According to Period of Prenatal Antidepressant Exposure: A Systematic Review and Meta-analysis

Mezzacappa A¹, Lasica PA¹, Gianfagna F², Cazas O¹, Hardy P³, Falissard B⁴, Sutter-Dallay AL⁵, Gressier F³.

Author information

1

Department of Psychiatry, Assistance Publique-Hôpitaux de Paris, Bicêtre University Hospital, Le Kremlin Bicêtre, France.

2

EPIMED Research Centre-Epidemiology and Preventive Medicine, Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy3Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy.

3

Department of Psychiatry, Assistance Publique-Hôpitaux de Paris, Bicêtre University Hospital, Le Kremlin Bicêtre, France4Université Paris-Saclay, Univ Paris-Sud, UVSQ, CESP, INSERM U1178, Bicêtre University Hospital, Le Kremlin Bicêtre, France.

4

Université Paris-Saclay, Univ Paris-Sud, UVSQ, CESP, INSERM U1178, Department of Biostatistics, Maison de Solenn, Paris, France.

5

Research Center INSERM 1219, Bordeaux Population Health Bordeaux University, University Department of Adult Psychiatry, Charles-Perrens Hospital, Bordeaux, France.

Abstract

Importance:

Several studies have examined the links between prenatal exposure to antidepressants and autism spectrum disorders (ASDs) in children, with inconsistent results, especially regarding the impact of the trimester of exposure.

Objective:

To perform a systematic review of the literature and a meta-analysis of published studies to assess the association between ASDs and fetal exposure to antidepressants during pregnancy for each trimester of pregnancy and preconception.

Data Sources:

PubMed, EMBASE, and PsycINFO databases up to May 2016 were searched in June 2016 for observational studies. For the meta-analyses, data were analyzed on RevMan version 5.2 using a random-effect model. For the review, studies were included if they had been published and were cohort or case-control studies, and for the meta-analysis, studies were included if they were published studies and the data were not derived from the same cohorts.

Study Selection:

We included all the studies that examined the association between ASDs and antenatal exposure to antidepressants.

Data Extraction and Synthesis:

Three reviewers independently screened titles and abstracts, read full-text articles, and extracted data. The quality of the studies was also assessed.

Main Outcomes and Measures:

Primary outcome was the association between antidepressants during pregnancy and ASDs. Secondary outcomes were the associations between antidepressants in each individual trimester or before pregnancy and ASDs.

Results:

Our literature search identified 10 relevant studies with inconsistent results. For prenatal exposure, the meta-analysis on the 6 case-control studies (117 737 patients) evidenced a positive association between antidepressant exposure and ASDs (odds ratio [OR], 1.81; 95% CI, 1.49-2.20). The association was weaker when controlled for past maternal mental illness (OR, 1.52; 95% CI, 1.09-2.12). A similar pattern was found whatever the trimester of exposure considered (first trimester: OR, 2.09, 95% CI,1.66-2.64; second: OR, 2.00, 95% CI, 1.55-2.59; and third: OR, 1.90, 95% CI, 1.20-3.02. Controlled for past maternal mental illness: first trimester: OR, 1.79; 95% CI, 1.27-2.52, second: OR, 1.67, 95% CI, 1.14-2.45; and third: OR, 1.54, 95% CI, 0.82-2.90). No association was found when the 2 cohort studies were pooled (772 331 patients) for the whole pregnancy (hazard ratio, 1.26; 95% CI, 0.91-1.74) or for the first trimester. In addition, preconception exposure to antidepressants was significantly associated with an increased risk for ASDs (OR controlled for past maternal illness, 1.77; 95% CI, 1.49-2.09).

Conclusions and Relevance:

There is a significant association between increased ASD risk and maternal use of antidepressants during pregnancy; however, it appears to be more consistent during the preconception period than during each trimester. Maternal psychiatric disorders in treatment before pregnancy rather than antenatal exposure to antidepressants could have a major role in the risk for ASDs. Future studies should address the problem of this potential confounder.

PMID: 28418571

DOI: 10.1001/jamapediatrics.2017.0124

La testostérone prénatale des progéniteurs pourrait être impliquée dans l'étiologie à la fois de l'anorexie mentale et des troubles du spectre autistique de leur progéniture

Traduction: G.M.

Am J Hum Biol. 2014 Nov;26(6):863-6. doi: 10.1002/ajhb.22597. Epub 2014 Jul 31.

Prenatal testosterone of progenitors could be involved in the etiology of both anorexia nervosa and autism spectrum disorders of their offspring

Romero-Martínez A¹, Moya-Albiol L.

Author information

• ¹Psychobiology Department, University of Valencia, Valencia, Spain.

Abstract

OBJECTIVES:

High intrauterine testosterone (T) levels seem to play a role in the development of autism spectrum disorders (ASDs), but their role in anorexia nervosa (AN) is controversial. Parents with masculinized 2D:4D ratios, a marker of the organizational effects of T, may have other relevant biological characteristics, in particular exposing their offspring to high T levels in the prenatal environment. This would increase the likelihood of their offspring developing these disorders.
Les haut niveaux de testostérone intra-utérin (T) semblent jouer un rôle dans le développement des troubles du spectre autistique (TSA), mais leur rôle dans l'anorexie mentale (AN) est controversé. Les parents ayant un indice de Manning différent de un, un marqueur des effets organisationnels de T, peuvent avoir d'autres caractéristiques biologiques pertinentes, en particulier exposer leur progéniture à des niveaux élevés en T dans l'environnement prénatal. Cela permettrait d'accroître la probabilité de leur progéniture développer ces affections.

METHODS:

The present study examined whether parents of offspring with AN (n=34; mean age= 51) and ASD (n=36; mean age=45) differ from control parents (n=40; mean age=43) in 2D:4D ratio, as well as by salivary T levels and its relationships.

RESULTS:

Our results revealed that AN and ASD parents (fathers and mothers) have masculinized 2D:4D ratios of the right hand compared to control parents. However, the difference compared to controls was larger in the ASD than the AN group. Furthermore, current salivary T levels were negatively related to the 2D:4D ratio in ASD and AN parents only.
Nos résultats ont révélé que les parents AN et TSA  (pères et mères) ont ration 2D: 4D masculinsé de la main droite par rapport aux parents du groupe contrôle. Cependant, la différence par rapport aux témoins était plus grande avec le groupe TSA qu'avec le groupe AN. En outre, les niveaux T salivaires courants ont été négativement liés au ratio 2D: 4D chez les parents TSA et AN seulement.

CONCLUSIONS:

Our data partially support the view of high prenatal masculinization as a potential intermediate phenotype to the development of these disorders in their offspring. 
Nos données confirment partiellement l'idée d'une haute masculinisation prénatale comme un phénotype intermédiaire potentiel pour le développement de ces troubles dans la progéniture. 

Am. J. Hum. Biol. 26:863-866, 2014. © 2014 Wiley Periodicals, Inc.
© 2014 Wiley Periodicals, Inc.

PMID: 25130276