THU466 XLH During Pregnancy: A Closer Look Based On Real-World Experience
Bibliographic record
Abstract
Abstract Disclosure: D.S. Ali: None. A.A. Khan: Advisory Board Member; Self; Amgen Inc, Takeda. Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Radius Health, Inc, Takeda, Ultragenyx. Background: X-linked hypophosphatemia (XLH) is a genetic disorder caused by mutation in the PHEX gene leading to excess serum levels of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23). High FGF23 causes renal phosphate wasting, decreased production of serum 1,25-dihydroxy vitamin D, and increased metabolism of 1,25-dihydroxy vitamin D, leading to hypophosphatemia. Maintaining normal serum phosphorus levels in pregnant women with XLH is critically important to ensure mineralization of the fetal skeleton. Multiple factors may influence phosphorus homeostasis in pregnancy, including an increase in PTHrP production and a tripling of calcitriol beginning in the first trimester. Case study: 30 years old Gravida 1 Para 0 with XLH, diagnosed at the age of 18 months. She has a pathogenic heterozygous mutation of the PHEX gene (c.1645+1G>A). Treated with phosphate and calcitriol since diagnosis. Had no history of neonatal seizure or respiratory distress, and no dental or renal manifestations. No prior fractures or corrective surgeries and has a normal BMD. No history of enthesopathy, however, has chronic joint pain > 1 year. The pregnancy progressed well with no issues; the patient chose not to undergo amniocentesis for fetal diagnosis. She was monitored closely every 3 weeks, aiming to maintain the serum phosphorus within the normal range to ensure adequate mineralization of the fetal skeleton. The requirements for phosphate increased by 50% in the 2nd trimester and by 125% in the 3rd trimester compared to baseline. While the calcitriol dose increased by 25% in the 3 trimesters compared to baseline. Because further increases in the calcitriol dose were associated with hypercalciuria, the dose was carefully titrated. The mean serum phosphorus level was maintained in the low normal reference range at 0.79 - 0.8 mmol/L (NR: 0.8-1.45), mean TmP/GFR 0.611 (NR: 0.96-1.44). She was induced at 37 weeks due to cholestasis, and delivered with a vaginal delivery. The baby boy weighed 2.690 kg and had slightly low serum phosphorus and calcium levels at birth, which corrected spontaneously. DNA analysis confirmed that the baby also has a pathogenic mutation of the PHEX gene. Conclusion: There was a noticeable variation in the serum phosphorus levels during the 1st and 2nd trimesters and less so in the 3rd trimester and during lactation. The dose of phosphate and active vitamin D required careful upward titration to maintain a normal serum phosphorus level. Therefore, close monitoring is essential. Although the rate of c-sections is higher (76%) amongst the XLH patient population compared to the normal population 27.1%, our patient delivered vaginally with no adverse skeletal outcomes in the mother or neonate. Presentation: Thursday, June 15, 2023
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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 | 0.001 |
| 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".