Altered placental phenotype and increased risk of placental pathology in fetal spina bifida: a matched case-control study
Bibliographic record
Abstract
Abstract Open spina bifida (SB) remains one of the most common congenital anomalies and associates with significant comorbidities in the fetus, which may, in part, be driven by placental maldevelopment. We hypothesised that placental pathologies and maldevelopment would be more prevalent in fetuses with SB compared to fetuses without congenital anomalies. Placental histopathology (H&E-stained slides) and transcriptome (Clariom D™ microarray) were evaluated for fetuses with isolated open SB undergoing either pregnancy terminations or term deliveries (cases; n=12) and control fetuses without congenital anomalies having term or preterm births (n=22). Associations between study group and placental histopathology were adjusted for fetal sex and gestational age [GA] at delivery. Relationships between placental histopathology and select placental gene expression signatures were also evaluated. Case placentae had lower placental weight than controls (median [IQR]: 263g [175, 370] vs. 455 [378, 560], p=0.001). Placental villi structural phenotype was different in cases, who had a higher proportion of immature intermediate villi than controls (32.5% [6.3, 56.3] vs. 10% [5, 13.8], p=0.01), but similar proportions of mature intermediate (10% [5, 10] vs. 10% [8.75, 11.25]) and terminal villi (22.5% [11.3, 43.8] vs. 30 [20, 36.3]), and similar odds of having many syncytial knots (adjusted odds ratio [aOR]=6 [0.2, 369]) as full-term born controls. Cellular phenotypic differences in case placentae included higher odds of having many Hofbauer cells (aOR=16.2 [1.4, 580], p=0.02) and a thick syncytial membrane (aOR=146 [3, 3.46e5], p=0.007). Expression in gene pathways related to immune/inflammatory processes, spinal cord injury, and Hedgehog and Wnt signaling were associated with placental maturity in cases. This study is the first to characterize placental histopathology in a contemporary cohort of fetuses with SB. Improved knowledge on placental histopathological and genetic phenotypes in spina bifida increases our understanding of mechanisms that may drive comorbidities to ultimately reduce offspring morbidity and mortality.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| 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".