SAT-726 - Effects of burosumab during pregnancy in a XLH woman: report of a successful case

During pregnancy, multiple physiological mechanisms are activated to ensure adequate maternal–fetal nutrient transfer, with the placenta playing a central role. In women with X-linked hypophosphatemia (XLH), maternal hypophosphatemia represents a clinical and therapeutic challenge, with potential consequences for both the mother and the fetus. Burosumab is a new treatment for XLH disease. Animal studies have reported no teratogenic effects but increased late fetal loss and preterm births, associated with maternal hyperphosphatemia, at doses 15-fold the expected human exposure. There are no clinical data available on the effects of this drug on human fertility.
Clinical case: A 25 y.o. woman diagnosed with XLH at age 2, was treated with phosphate and calcitriol until age 20, when burosumab was initiated. Three years later, she conceived, discontinued burosumab, and resumed conventional therapy. A miscarriage occurred at week 11, after which burosumab was restarted. Despite contraception counseling, she conceived again 4 months later, discontinued burosumab, and resumed phosphate and calcitriol. The pregnancy progressed without major complications. Phosphate supplementation was increased by up to 70%, limited by gastrointestinal intolerance, and calcitriol was increased by 50% in late gestation. Fasting serum phosphate remained low, while serum and urinary calcium levels were stable. Delivery was by cesarean section at week 35. The male neonate (2,015 g; 50 cm) developed hypophosphatemia on day 2, with a confirmed PHEX mutation. Echocardiography showed pulmonary stenosis and patent ductus arteriosus, requiring surgery. Breastfeeding continued for six months before she resumed burosumab due to severe pain. Two years later, while receiving burosumab, a new pregnancy test was positive, and fetal ultrasound confirmed a single viable fetus consistent with 9 weeks of gestation. Burosumad was discontinued and conventional therapy was resumed. The patient developed transient perioral and acral cyanosis; extensive evaluation excluded cardiac, pulmonary, and rheumatologic disease, and symptoms spontaneously resolved at six months of gestation. The remainder of the pregnancy was uneventful, with persistently low phosphate and normal calcium parameters. Supplementation doses of phosphate and calcitriol were similar to those used in the previous pregnancy. Delivery occurred by cesarean section at week 37, a healthy female neonate was born (2,815 g; 48 cm). Breastfeeding was maintained for two months before the mother restarted burosumab due to severe joint and muscle pain.

Conclusion: This case represents the first reported pregnancy in a woman with XLH exposed to burosumab during the first trimester. These findings suggest potential safety around conception and no teratogenic effects in the fetus; however, further real-world evidence is needed to support these findings.

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