Sex-specific associations between placental corticotropin releasing hormone and problem behaviors in childhood
Bibliographic record
Abstract
Placental corticotropin-releasing hormone (pCRH) is a neuroactive peptide produced in high concentrations in mid-late pregnancy, during key periods of fetal brain development. Some evidence suggests that higher pCRH exposure during gestation is associated with adverse neurodevelopment, particularly in female offspring. In 858 mother-child dyads from the sociodemographically diverse CANDLE cohort (Memphis, TN), we examined: (1) the slope of pCRH rise in mid-late pregnancy and (2) estimated pCRH at delivery as a measure of cumulative prenatal exposure. When children were 4 years-old, mothers reported on problem behaviors using the Child Behavior Checklist (CBCL) and cognitive performance was assessed by trained psychologists using the Stanford-Binet Intelligence Scales. We fitted linear regression models examining pCRH in relation to behavioral and cognitive performance measures, adjusting for covariates. Using interaction models, we evaluated whether associations differed by fetal sex, breastfeeding, and postnatal neighborhood opportunity. In the full cohort, log-transformed pCRH measures were not associated with outcomes; however, we observed sex differences in some models (interaction p-values≤0.01). In male offspring, an interquartile (IQR) increase in pCRH slope (but not estimated pCRH at delivery), was positively associated with raw Total (β=3.06, 95%CI: 0.40, 5.72), Internalizing (β=0.89, 95%CI: 0.03, 1.76), and Externalizing (β=1.25, 95%CI: 0.27, 2.22) Problem scores, whereas, in females, all associations were negative (Total Problems: β=-1.99, 95%CI: -3.89, -0.09; Internalizing: β=-0.82, 95%CI: -1.42, -0.23; Externalizing: β=-0.56, 95%CI: -1.34, 0.22). No associations with cognitive performance were observed nor did we observe moderation by breastfeeding or postnatal neighborhood opportunity. Our results provide further evidence that prenatal pCRH exposure may impact subsequent child behavior in sex-specific ways, however in contrast to prior studies suggesting adverse impacts in females, steeper mid-gestation pCRH rise was associated with more problem behaviors in males, but fewer in females.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".