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Des folates pendant la grossesse pour prévenir l’autisme ? (Dr. Alexandre Haroche, Journal International de Médecine)

Une supplémentation en acide folique avant et pendant la grossesse est recommandée et en pratique très largement proposée afin de prévenir le risque de malformations du tube neural. La question demeure de l’intérêt éventuel de cette médication sur la prévention d’autres pathologies liées au développement cérébral, et cette question a été posée en particulier pour l’autisme. Dans ce domaine, on dispose essentiellement de deux publications : l’une, norvégienne, a pu montrer une diminution du risque d’autisme tandis que l’autre, danoise, n’a pas retrouvé d’effet bénéfique d’une supplémentation pour prévenir ce trouble. Quittons la Scandinavie, et voyons ce qu’il en est dans cette grande étude israélienne qui sera publiée bientôt dans JAMA Psychiatry.

Les auteurs ont tiré parti d’une large cohorte incluant 35 % de la population israélienne de moins de 15 ans. Ils ont pu ainsi comparer l’ensemble des cas de trouble du spectre autistique et environ un tiers des enfants nés entre 2003 et 2007 (et suivis jusqu’en 2015). La supplémentation en folates est recommandée en Israël avant et pendant la grossesse. La prise du traitement était évaluée à l’aide d’un registre rassemblant les données sur la dispensation des médicaments dans la plupart des pharmacies du pays depuis 1996.

Un risque d’autisme 3,7 fois moindre

Sur 45 300 enfants nés de 26 702 mères, 572 ont reçu un diagnostic d’autisme (1,3 %). On retrouvait une exposition aux folates et/ou aux multivitamines avant la grossesse dans 11 917 cas (26,3 %) et pendant la grossesse dans 21 884 cas (48,3 %). Les résultats ont été ajustés sur le sexe, l’année de naissance, le niveau socio-économique, la présence d’un diagnostic psychiatrique chez un des deux parents ainsi que leurs âges et le nombre de grossesse. Les « multivitamines » dont il est ici question n’ont pas pu être précisées dans cette étude (reposant sur des codes renseignés en pharmacie), cependant on ne peut exclure qu’une partie de ces préparations contiennent également des folates.

Le risque relatif d’autisme après exposition aux folates et/ou aux multivitamines avant la grossesse a été estimé à 0,41 (intervalle de confiance à 95 % [IC95] 0,32 à 0,53) et 0,39 (IC 95 0,30 à 0,50) après ajustement. Lorsque les mères prenaient les folates durant la grossesse, le risque est encore plus diminué : 0,27 (IC95 0,22 à 0,34) après ajustement (soit 3,7 fois moins).

Si l’on s’intéresse uniquement aux folates, on obtient, avec une exposition avant la grossesse un risque relatif de 0,62 (IC95 0,47 à 0,83), soit 0,56 (IC95 0,42 à 0,74) après ajustement. L’exposition durant la grossesse a été associée à un risque relatif de 0,34 (IC95 0,27 à 0,43) et 0,32 (IC95 0,26 à 0,41) après ajustement. Les multivitamines sans supplémentation en folates associée avant la grossesse permettraient une diminution du risque d’autisme de 0,36 (IC 95 0,24 à 0,52) après ajustement, et 0,35 (IC95 0,28 à 0,44) si pris durant la grossesse.

Faut-il enrichir l’alimentation en folates ?

L’exposition maternelle aux vitamines et aux folates avant la grossesse ne semble pas diminuer le risque d’autisme chez les filles (du moins avant ajustement), mais, selon les auteurs, l’analyse manquait probablement de puissance. Le risque n’était pas modifié chez les enfants de femmes ayant pris des folates ou des vitamines, mais conservant une carence vitaminique. Autrement dit, il est peu probable que cette proportion d’autisme relativement plus bas chez les femmes prenant des folates ou des vitamines soit uniquement due à des facteurs confondant (par exemple de type socio-économiques), car ces femmes qui conservent une carence « bénéficieraient » également de ce biais de confusion.

Cette étude souligne, s’il était besoin, le lien étroit entre l’autisme et les mécanismes infiniment complexes régissant le développement cérébral. Mais aussi complexes que soient ces phénomènes, il semble donc, si l’on en croit cette étude, qu’une mesure simple et très facilement accessible puisse prévenir un des troubles neuropsychiatriques les plus graves.

Pour rappel, on recommande en France la prise de folates à 400 mg par jour à partir de 4 semaines avant et jusqu’à 8 semaines après la date présumée de la conception. Pour les femmes « à risque », c’est-à-dire essentiellement pour celles qui bénéficient d’un traitement anti-épileptique, on recommande une supplémentation de 5 mg/j durant la même période. Depuis 1998, les farines sont supplémentées en folates aux États-Unis et au Canada. Une telle publication pourrait inciter les pouvoirs publics à introduire cette mesure de santé publique en France.
Dr Alexandre Haroche

Référence
Levine SZ et coll. : Association of Maternal Use of Folic Acid and Multivitamin Supplements in the Periods Before and During Pregnancy With the Risk of Autism Spectrum Disorder in Offspring. JAMA Psychiatry. 2018 ; publication avancée en ligne le 3 janvier. doi: 10.1001/jamapsychiatry.2017.4050.

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    References:

    JBHNews

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