gms | German Medical Science

Introduction: The use of medication during pregnancy carries a potential health risk for the unborn child. However, the majority of drugs examined in previous observational studies have shown inconsistent results with the risk of childhood cancer, and these findings have not been consolidated in drug-specific meta-analyses.

Methods: To address this gap, a systematic search was conducted in the databases PubMed and Science Citation Index for studies on medication use during pregnancy and the risk of childhood cancer. Meta-analyses with estimates for random effects models with 95% confidence intervals were conducted, if at least three studies on the same research question were available. The I² statistic was calculated to quantify between-study heterogeneity. Statistical significance of I2 was analyzed with the Q statistic (P value for heterogeneity (P)). Study quality was summarized based on a self-developed scoring system with eight items.

Results: The systematic literature search yielded 2,373 studies, of which 62 were included in the systematic review. We conducted a total of 48 analyses including exposure to 13 different types of medications during pregnancy and 8 different childhood cancer sites. Pooled odds ratios (OR) showed an increased risk of acute leukemia (AL) and its subtype acute lymphoblastic leukemia (ALL) after prenatal exposure to antiemetics (AL: OR= 1.46 (95 % confidence interval 1.04; 2.05) I²= 0.0 % P= 0.64; ALL: OR= 1.27 (1.01; 1.59) I²= 0.0 % P= 0.93) and any kind of antibiotics (AL: OR= 1.13 (1.01; 1.27) I²= 0.0 % P= 0.53; ALL: OR= 1.11 (1.01; 1.23) I²= 15.8 % P= 0.29). In addition, an increased risk of childhood cancer in general was observed when mothers took nitrosatable antibiotics (OR= 1.32 (1.13; 1.55) I²= 0.0 % P= 0.98). Children prenatally exposed to hormones of any kind showed an increased risk of AL (OR= 1.47 (1.02; 2.13) I2= 66.7 % P= 0.01). Furthermore, analyses revealed an increased risk of ALL after prenatal exposure to oral contraceptives (OR= 1.29 (1.02; 1.63) I2= 0.0 % P= 0.53). Moreover, maternal intake of vitamin supplements showed a decreased risk of AL (OR= 0.72 (0.54; 0.96) I2= 46,3 % P= 0.16) and CNS tumors (OR= 0.77 (0.62; 0.96) I²= 67.2 % P= 0.002). Finally, the use of analgesics (OR= 1.40 (1.00; 1.95) I²= 43.8 % P= 0.15) during pregnancy was associated with an increased risk of neuroblastoma in the offspring. The remaining 38 analyses showed no association.

Discussion: Our results suggest that the use of nitrosatable antibiotics during pregnancy may be associated with an increased risk of childhood cancer. Maternal intake of antibiotics, antiemetics and hormones may increase the risk of AL and ALL in their children. An increased risk of childhood neuroblastoma could be associated with prenatal exposure to analgesics. Furthermore, maternal use of vitamin supplements during pregnancy might decrease the risk of AL and CNS tumors in children. However, the underlying disease of the mother, which is treated with the investigated medication, could be the actual reason for the development of childhood cancer in the offspring.

The authors declare that they have no competing interests.

The authors declare that an ethics committee vote is not required.

The contribution has already been published: The abstract was published in the Proceedings of the American Association for Cancer Research Annual Meeting 2024 [1], but was not presented.