Predictive utility of placental hypothalamic–pituitary–adrenal axis biomarkers and infant neurodevelopment
Notice bibliographique
Résumé
Alcohol use remains common in pregnancy with prenatal alcohol exposure (PAE) associated with a plethora of adverse outcomes, including impaired emotional regulation and stress reactivity. Prior preclinical studies and emerging clinical evidence indicate that PAE affects the fetal hypothalamic-pituitary-adrenal (HPA) axis via the maternal-fetal interface in the placenta; however, little is known about the effect of these alterations on neurodevelopmental outcomes. We earlier reported on the effect of PAE and maternal stress on HPA axis biomarkers in placenta and umbilical cord (UC) blood; in the current study, we examined the effect of HPA axis biomarkers on infant neurodevelopmental outcomes at 6-9 months of term-equivalent age. Participants in the Ethanol, Neurodevelopment, Infant and Child Health (ENRICH-2) prospective cohort were followed from the second trimester of pregnancy until infants were 6-9 months of term-equivalent age. Maternal alcohol use was assessed through prospective interviews and a battery of ethanol biomarkers; maternal stress, by a Perceived Stress Scale (PSS). Placenta and UC blood specimens were collected shortly after birth, flash frozen, and analyzed for mRNA and protein expression of placental corticotropin-releasing hormone (pCRH), hydroxysteroid 11-beta dehydrogenase types 1 and 2 (HSD11B1, HSD11B2) and corresponding proteins (11β-HSD1 and 11β-HSD2), and Nuclear receptor subfamily 3 Group C Member 1-alpha (NR3C1-α) and corresponding glucocorticoid receptor alpha. UC plasma cortisol and cortisone levels were measured with ELISA. Bayley Scales of Infant Development, fourth edition (BSID-4; Motor, Language, Cognitive scores) and Infant Behavior Questionnaire Revised (IBQ-R; Surgency, Orienting/Regulation, Negative Affect) assessed neurodevelopment at 6-9 months of term-equivalent age. Pearson correlation was used to examine associations between placental HPA axis biomarkers and neurodevelopmental outcomes overall and after stratification by group (Alcohol/Control). Multivariable linear regression assessed the independent effect of placental biomarkers and Alcohol * biomarker interactions on infant outcomes after adjusting for Alcohol and maternal stress. Participants (32 Alcohol and 68 Controls) were comparable in sociodemographic characteristics. Activation of the placental HPA axis was correlated with a decrease in BSID-4 scores among Controls and an increase in IBQ-R scores (Surgency and Negative Affect) among Alcohol participants. In multivariable analyses, the HSD11B2/HSD11B1 ratio was associated with a decrease in Cognitive scores, and the Alcohol * pCRH interaction was associated with a decrease in Orienting/Regulation and an increase in Surgency and Negative Affect (all p's < .05), after adjusting for Alcohol and PSS. A significant independent effect of PSS was also observed on infant motor skills, Orienting/Regulation, and Negative Affect. This is the first clinical study to characterize the role of placental HPA axis biomarkers and maternal psychosocial stress in PAE-induced changes on infant neurodevelopment, highlighting the importance of a "placenta-brain axis". We demonstrated that the effects of mild-to-moderate PAE on infant neurobehavior were observed in participants with the highest quartile of pCRH expression, emphasizing the role of placental biomarkers in PAE-induced effects.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».