Langerhans cell histiocytosis in children born after assisted reproductive technology

Research question: Are children born after assisted reproductive technology (ART) at higher risk of developing Langerhans cell histiocytosis (LCH)?

Design: Records of children born after ART recorded by the UK Human Fertilisation & Embryology Authority were linked to National Registry of Childhood Tumours records to determine the number of children developing LCH. Calculated person-years at risk were used in conjunction with the incidence of LCH in the general population to determine the expected number of cases if the cohort had the same incidence as the general population with similar age and sex, over the same calendar years. The standardized incidence ratio (SIR) was derived as the ratio of observed to expected cases. Exact 95% CI were calculated.

Results: In total, 118,155 children born after ART contributed 796,633 person-years follow-up (average follow-up 6.74 years). Eight cases of LCH were identified, compared with 3.75 cases expected (SIR 2.135, 95% CI 0.92-4.21; P = 0.074). Significantly more cases were associated with intracytoplasmic sperm injection (ICSI) (SIR 4.02, 95% CI 1.31-9.39) and male factor infertility (SIR 5.41, 95% CI 1.47-13.84). Most cases of LCH had single-system disease (n = 6).

Conclusions: This study found that significantly more cases of LCH were identified in children born after ICSI and in children whose parents had male factor infertility. A non-significant excess of cases in children born after ART was identified. Absolute excess risk was small. Given the rarity of LCH and the small number of cases included in this large cohort, further studies into the risk of LCH in children born after ART are indicated.